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Hult, Andreas, Med Dr
Biography [eng]

Researcher in Public Health with main focus on physical activity, lifestyle and a healthy aeging.

Biography [swe]

Forskare i folkhälsa med fokus på fysisk aktivitet, livsstil och ett hälsosamt åldrande.

Publications (10 of 13) Show all publications
Ballin, M., Lundberg, E., Sörlén, N., Nordström, P., Hult, A. & Nordström, A. (2019). Effects of interval training on quality of life and cardiometabolic risk markers in older adults: a randomized controlled trial. Clinical Interventions in Aging, 14, 1589-1599
Open this publication in new window or tab >>Effects of interval training on quality of life and cardiometabolic risk markers in older adults: a randomized controlled trial
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2019 (English)In: Clinical Interventions in Aging, ISSN 1176-9092, E-ISSN 1178-1998, Vol. 14, p. 1589-1599Article in journal (Refereed) Published
Abstract [en]

Purpose: To explore the effects of 10 weeks of progressive vigorous interval training as a single intervention on health-related quality of life (HRQoL) and cardiometabolic risk markers in centrally obese 70-year-old individuals.

Participants and methods: A randomized controlled trial (ClinicalTrials.gov registration no. NCT03450655) including seventy-seven community-dwelling 70-year-old men and women with central obesity defined as > 1 kg visceral adipose tissue for women and > 2 kg for men. Participants randomized to the intervention group were offered a 10-week progressive vigorous interval training program performed three times per week. Control subjects were asked to maintain their daily living and routines throughout the trial. All participants in both groups had received tailored lifestyle recommendations focused on diet and physical activity at one occasion within 12 months prior to trial initiation. Prespecified outcome measures included: changes in HRQoL using the Short Form Health Survey Questionnaire (SF-36), blood pressure; resting heart rate (HR) and blood lipids. All analyses were conducted on an intention-to-treat basis.

Results: The intervention resulted in significant effects on the SF-36 mental component summary (MCS) score and the mental health (MH) subscale (P< 0.05 for both), when compared to the control group. Specifically, the intervention group increased their MCS score by 6.3 points (95% confidence interval [CI] = 0.3–12.3) and their MH score by 6.0 points (95% CI = 1.7–10.4) compared to the control group. Moreover, significant effects were seen on resting HR, total cholesterol and LDL-cholesterol (P<0.05 for all).

Conclusion: It was shown that 10 weeks of vigorous interval training as a single intervention was sufficient to improve mental aspects of HRQoL in older individuals with central obesity, which is a critical aspect of healthy ageing. Positive effects were seen also on cardiometabolic risk markers.

Place, publisher, year, edition, pages
Dove Press, 2019
Keywords
ageing, blood lipids, exercise, perceived health
National Category
Physiotherapy
Identifiers
urn:nbn:se:umu:diva-163731 (URN)10.2147/CIA.S213133 (DOI)000484757900001 ()31564841 (PubMedID)2-s2.0-85072746002 (Scopus ID)
Available from: 2019-10-02 Created: 2019-10-02 Last updated: 2019-11-14Bibliographically approved
Ballin, M., Lundberg, E., Sörlén, N., Nordström, P., Hult, A. & Nordström, A. (2019). Effects of Interval Training on Visceral Adipose Tissue in Centrally Obese 70-Year-Old Individuals: A Randomized Controlled Trial. Journal of The American Geriatrics Society, 67(8), 1625-1631
Open this publication in new window or tab >>Effects of Interval Training on Visceral Adipose Tissue in Centrally Obese 70-Year-Old Individuals: A Randomized Controlled Trial
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2019 (English)In: Journal of The American Geriatrics Society, ISSN 0002-8614, E-ISSN 1532-5415, Vol. 67, no 8, p. 1625-1631Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To investigate the effects of 10 weeks of progressive vigorous-intensity interval training as a single intervention on body composition among 70-year-old individuals with central obesity.

DESIGN: Randomized controlled trial (ClinicalTrials.gov registration No. NCT03450655).

SETTING: Community-dwelling 70-year-old men and women living in the Umeå municipality in Sweden.

PARTICIPANTS: Seventy-seven 70-year-old men and women with central obesity (greater than 1 kg visceral adipose tissue [VAT] for women and greater than 2 kg VAT for men).

INTERVENTION: Participants allocated to the intervention group were offered a 10-week progressive concurrent exercise program performed three times per week. All participants in both groups had received tailored lifestyle recommendations focused on diet and physical activity at one occasion within 12 months prior to trial initiation.

MEASUREMENTS: The primary outcome was changes in VAT, and secondary outcomes included changes in total fat mass (FM), total lean body mass (LBM), and body mass index.

RESULTS: Comparing the groups, there were no significant differences in decrease of VAT mass (P = .10), although the intervention group significantly decreased FM by 716 g (P = .01) and gained LBM by 508 g (P = .03), compared to the control group. Furthermore, the effects of the training were significantly greater in the male subcohort (P < .05 for interaction), with positive effects also on VAT and FM, where men in the intervention group decreased VAT by 175 g (P < .05) and FM by 1364 g (P = .004), compared to the male controls.

CONCLUSIONS: The present trial demonstrates that 10 weeks of progressive vigorous interval training is sufficient to significantly decrease FM in older adults with central obesity, with positive effects also on LBM.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
Keywords
exercise, lean body mass, visceral fat
National Category
Geriatrics Gerontology, specialising in Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-158499 (URN)10.1111/jgs.15919 (DOI)000478919000014 ()31012497 (PubMedID)
Available from: 2019-04-29 Created: 2019-04-29 Last updated: 2019-09-02Bibliographically approved
Vikberg, S., Sörlén, N., Brandén, L., Johansson, J., Nordström, A., Hult, A. & Nordström, P. (2019). Effects of Resistance Training on Functional Strength and Muscle Mass in 70-Year-Old Individuals With Pre-sarcopenia: A Randomized Controlled Trial. Journal of the American Medical Directors Association, 20(1), 28-34
Open this publication in new window or tab >>Effects of Resistance Training on Functional Strength and Muscle Mass in 70-Year-Old Individuals With Pre-sarcopenia: A Randomized Controlled Trial
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2019 (English)In: Journal of the American Medical Directors Association, ISSN 1525-8610, E-ISSN 1538-9375, Vol. 20, no 1, p. 28-34Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Sarcopenia has been defined as age-related loss of muscle mass and function. The aim of this randomized controlled trial was to examine the effects of a 10-week instructor-led resistance training program on functional strength and body composition in men and women aged 70 years with pre-sarcopenia.

DESIGN, SETTING, AND PARTICIPANTS: Participants were randomized to either 10 weeks of a physical training regimen including optional nutritional supplementation (n = 36) or to a control group (n = 34) (ClinicalTrials.gov, no. NCT03297632). The main outcome was changes in the Short Physical Performance Battery (SPPB) score. Secondary outcomes included the Timed Up and Go test, chair sit-stand time, lean body mass, and fat mass.

RESULTS: The intervention had no significant effect on SPPB in the total cohort (P = .18), when comparing changes in the intervention group with the control group. However, those given the intervention in the male subcohort increased 0.5 ± 0.4 (mean ± standard error for the difference) points in SPPB during follow-up (P = .02) compared to male controls. With respect to secondary outcomes, the intervention group decreased 0.9 ± 0.6 seconds in chair sit-stand time compared to controls (P = .01). Furthermore, the intervention resulted in significantly greater improvements for the training group than control group in all measures of body composition (P ≤ .01 for all). For example, lean body mass increased by a mean of 1147 ± 282 g (P < .001), and total fat mass decreased by a mean of 553 ± 225 g (P = .003), favoring the intervention group.

CONCLUSION/IMPLICATIONS: The main finding of this intervention study is that an easy-to-use, functional resistance training program was effective in maintaining functional strength and increasing muscle mass in older adults with pre-sarcopenia.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Resistance training, functional strength, muscle mass
National Category
Physiotherapy Gerontology, specialising in Medical and Health Sciences Geriatrics
Identifiers
urn:nbn:se:umu:diva-153603 (URN)10.1016/j.jamda.2018.09.011 (DOI)000454138000005 ()30414822 (PubMedID)2-s2.0-85055969854 (Scopus ID)
Note

Available online 7 November 2018.

Available from: 2018-11-23 Created: 2018-11-23 Last updated: 2019-01-15Bibliographically approved
Hult, A., Johansson, J., Nordström, P. & Nordström, A. (2019). Objectively Measured Physical Activity in Older Adults With and Without Diabetes. Clinical Diabetes, 37(2), 142-149, Article ID cd180041.
Open this publication in new window or tab >>Objectively Measured Physical Activity in Older Adults With and Without Diabetes
2019 (English)In: Clinical Diabetes, ISSN 0891-8929, E-ISSN 1945-4953, Vol. 37, no 2, p. 142-149, article id cd180041Article in journal (Refereed) Published
Abstract [en]

Background: Increased physical activity (PA) is ordinated to increase glycemic control in subjects with diabetes. We evaluated objectively measured as well as self-reported PA in elderly individuals with and without diabetes.

Method: The study included 1872 community-dwelling individuals (49% women), all aged 70 years. Objective PA was measured by accelerometers worn for 1 week. Physical activity patterns in subjects with and without diabetes were evaluated using multivariable adjustable regression models.

Results: In the cohort 210 subjects (138 men and 72 women) were found to have diabetes. Self-reported PA showed a weak association with objective PA (r = 0.06, p = 0.01).  Individuals with known diabetes had fewer steps per day (mean 5,754) than those with detected diabetes at baseline (mean 6,359) or no diabetes (mean 7,375, all p < 0.05). A cut-off value of at least 6,000 steps per day discriminated best between individuals with and without diabetes (multi-adjusted odds ratio (OR), 0.50, 95% CI, 0.36–0.69), and overall step-count also showed the strongest correlation with objective visceral adipose tissue (VAT, β = 0.29, p < 0.001). In contrast, objectively measured PA in at least 10-minute bouts, as recommended by WHO, did not discriminate between individuals with a without diabetes (OR, 0.92, 95% CI, 0.66–1.28).

Conclusion: Despite recommendations given to subjects with diabetes, objectively measured PA was more than 20% lower in elderly individuals with diabetes. Daily step-counts was also associated with VAT, a potential mediator of the effects of PA.

Place, publisher, year, edition, pages
American Diabetes Association, 2019
National Category
Clinical Medicine Endocrinology and Diabetes
Research subject
Public health
Identifiers
urn:nbn:se:umu:diva-154288 (URN)10.2337/cd18-0041 (DOI)
Available from: 2018-12-14 Created: 2018-12-14 Last updated: 2019-06-12Bibliographically approved
Hallkvist, O. M., Johansson, J., Nordström, A., Nordström, P. & Hult, A. (2018). Dairy product intake and bone properties in 70-year-old men and women. Archives of Osteoporosis, 13(1), Article ID 9.
Open this publication in new window or tab >>Dairy product intake and bone properties in 70-year-old men and women
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2018 (English)In: Archives of Osteoporosis, ISSN 1862-3514, Vol. 13, no 1, article id 9Article in journal (Refereed) Published
Abstract [en]

SUMMARY: In the present population-based study including 70-year-old men and women, total dairy product intake was associated with a weak positive association with tibia trabecular and cortical cross-sectional areas.

PURPOSE: Milk consumption has recently been suggested to increase fracture risk. Therefore, we aimed to investigate associations between dairy product consumption and peripheral bone properties. Furthermore, we explored whether consumption of milk and fermented dairy products affected bone properties differently.

METHODS: The Healthy Aging Initiative is a population-based, cross-sectional study investigating the health of 70-year-old men and women. Out of the 2904 individuals who met the inclusion criteria, data on self-reported daily dairy product consumption (dl/day), peripheral quantitative computed tomography (pQCT) examinations at the 4 and 66% scan sites of the tibia and radius, and dual-energy X-ray absorptiometry (DXA) scans were collected from 2040 participants. Associations between dairy product consumption and bone properties were examined using multiple linear regression models adjusted for sex, muscle area, meal size, dietary protein proportion, current smoking status, and objectively measured physical activity.

RESULTS: Total dairy product intake was associated with larger trabecular (2.296 (95% CI, 0.552-4.039) mm2, per dl/day increase, p = 0.01) and cortical cross-sectional areas (CSAs) in the tibia (1.757 (95% CI, 0.683-2.830 mm2, p = 0.001) as measured by pQCT and higher areal bone mineral density (aBMD) of the radius (3.231 (95% CI, 0.764-5.698) mg/cm2, p = 0.01) as measured by DXA. No other measurement in the tibia, radius, femoral neck, or lower spine was associated significantly with dairy product intake. Bone properties did not differ according to the type of dairy product consumed.

CONCLUSION: No evidence of a negative association between dairy product consumption and bone health was found. Furthermore, total dairy product consumption was associated with increased CSAs in the tibia, regardless of dairy product type. Collectively, our findings indicate the existence of a weak but significant positive association between dairy product consumption bone properties in older adults.

Place, publisher, year, edition, pages
Springer, 2018
Keywords
Bone mineral density, Dairy product, Older adults, Peripheral quantitative computed tomography
National Category
Nutrition and Dietetics
Identifiers
urn:nbn:se:umu:diva-144507 (URN)10.1007/s11657-018-0420-1 (DOI)000423631300001 ()29380156 (PubMedID)
Available from: 2018-02-05 Created: 2018-02-05 Last updated: 2018-06-09Bibliographically approved
Johansson, J., Hult, A., Morseth, B., Nordström, A. & Nordström, P. (2018). Self-reported protein intake and properties of bone in community-dwelling older individuals. Archives of Osteoporosis, 13(1), Article ID 10.
Open this publication in new window or tab >>Self-reported protein intake and properties of bone in community-dwelling older individuals
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2018 (English)In: Archives of Osteoporosis, ISSN 1862-3514, Vol. 13, no 1, article id 10Article in journal (Refereed) Published
Abstract [en]

SUMMARY:This study revealed that a quick and simple estimation of protein intake was related to measures of bone density and area in 70-year-old individuals. Furthermore, these associations were mediated by muscle mass when investigating peripheral measurement sites such as arms and legs.

PURPOSE: Recent evidence suggests that dietary protein is beneficial for bone health in older individuals, but less is known about the influence of muscle mass on this relationship. This cross-sectional study aimed to investigate associations among protein intake, bone health, and muscle mass in 2332 men and women aged 70 years.

METHODS: Volumetric bone mineral density of the radius and tibia was measured using peripheral quantitative computed tomography. Using dual-energy X-ray absorptiometry, we measured areal bone mineral density (aBMD) at the L1-L4 vertebrae, radius, and femoral neck, together with appendicular lean mass. Participants reported their average meal size and proportion of meat/fish intake. Associations were investigated using multiple linear regression models, adjusted for multiple covariates.

RESULTS: Self-reported protein intake was associated with aBMD of the femoral neck (β = 0.082) and L1-L4 vertebrae (β = 0.063) in men (both p < 0.05) after adjusting for multiple covariates, including appendicular muscle mass. No significant association was detected among women. In addition, protein intake was associated with tibial cortical area (β = 0.08), periosteal circumference (β = 0.072), radial aBMD (β = 0.064), and trabecular area (β = 0.078) in men (all p < 0.05), although these associations were attenuated after adjustment for appendicular muscle mass (all p > 0.05).

CONCLUSION: Self-reported protein intake was associated with bone properties in 70-year-old men. The strength of these associations in peripheral bone sites may be partially mediated by muscle mass from protein intake.

Place, publisher, year, edition, pages
Springer, 2018
Keywords
Appendicular muscle mass, Bone mineral density, Community dwelling, Peripheral quantitative computed tomography, Protein intake
National Category
Nutrition and Dietetics
Identifiers
urn:nbn:se:umu:diva-144514 (URN)10.1007/s11657-018-0421-0 (DOI)000423810200001 ()29388047 (PubMedID)
Available from: 2018-02-05 Created: 2018-02-05 Last updated: 2018-06-09Bibliographically approved
Malm, C. B., Khoo, N. S., Granlund, I., Lindstedt, E. & Hult, A. (2016). Autologous Doping with Cryopreserved Red Blood Cells - Effects on Physical Performance and Detection by Multivariate Statistics. PLoS ONE, 11(6), Article ID e0156157.
Open this publication in new window or tab >>Autologous Doping with Cryopreserved Red Blood Cells - Effects on Physical Performance and Detection by Multivariate Statistics
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2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 6, article id e0156157Article in journal (Refereed) Published
Abstract [en]

The discovery of erythropoietin (EPO) simplified blood doping in sports, but improved detection methods, for EPO has forced cheating athletes to return to blood transfusion. Autologous blood transfusion with cryopreserved red blood cells (RBCs) is the method of choice, because no valid method exists to accurately detect such event. In endurance sports, it can be estimated that elite athletes improve performance by up to 3% with blood doping, regardless of method. Valid detection methods for autologous blood doping is important to maintain credibility of athletic performances. Recreationalmale (N = 27) and female (N = 11) athletes served as Transfusion (N = 28) and Control (N = 10) subjects in two different transfusion settings. Hematological variables and physical performance were measured before donation of 450 or 900 mL whole blood, and until four weeks after re-infusion of the cryopreserved RBC fraction. Blood was analyzed for transferrin, iron, Hb, EVF, MCV, MCHC, reticulocytes, leucocytes and EPO. Repeated measures multivariate analysis of variance (MANOVA) and pattern recognition using Principal Component Analysis (PCA) and Orthogonal Projections of Latent Structures (OPLS) discriminant analysis (DA) investigated differences between Control and Transfusion groups over time. Significant increase in performance (15 +/- 8%) and VO2max (17 +/- 10%) (mean +/- SD) could be measured 48 h after RBC re-infusion, and remained increased for up to four weeks in some subjects. In total, 533 blood samples were included in the study (Clean = 220, Transfused = 313). In response to blood transfusion, the largest change in hematological variables occurred 48 h after blood donation, when Control and Transfused groups could be separated with OPLS-DA (R-2 = 0.76/Q(2) = 0.59). RBC re-infusion resulted in the bestmodel (R-2 = 0.40/Q(2) = 0.10) at the first sampling point (48 h), predicting one false positive and one false negative. Over all, a 25% and 86% false positives ratio was achieved in two separate trials. In conclusions, autologous re-infusion of RBCs increased VO2max and performance as hypothesized, but hematological profiling by multivariate statistics could not reach the WADA stipulated false positive ratio of <0.001% at any time point investigated. A majority of samples remained within limits of normal individual variation at all times.

National Category
Sport and Fitness Sciences
Identifiers
urn:nbn:se:umu:diva-123974 (URN)10.1371/journal.pone.0156157 (DOI)000377564000009 ()27284981 (PubMedID)
Available from: 2016-07-07 Created: 2016-07-07 Last updated: 2018-06-07Bibliographically approved
Larsson, A., Hult, A., Nilsson, A., Olsson, M. & Oldenborg, P.-A. (2016). Red blood cells with elevated cytoplasmic Ca2+ are primarily taken up by splenic marginal zone macrophages and CD207+dendritic cells. Transfusion, 56(7), 1834-1844
Open this publication in new window or tab >>Red blood cells with elevated cytoplasmic Ca2+ are primarily taken up by splenic marginal zone macrophages and CD207+dendritic cells
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2016 (English)In: Transfusion, ISSN 0041-1132, E-ISSN 1537-2995, Vol. 56, no 7, p. 1834-1844Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The normal red blood cell (RBC) life span may be significantly reduced when RBCs are stored under blood bank conditions, resulting in a reduced 24-hour survival after transfusion. The damage of stored RBCs is probably multifactorial as stored RBCs share features of both senescence and suicidal RBC death (eryptosis). Since an increased intracellular Ca2+ concentration ([Ca2+](i)) is one key feature of eryptosis, we here investigated if stored human RBCs had increased [Ca2+](i) and the mechanisms behind uptake of such RBCs in a murine model.

STUDY DESIGN AND METHODS: The intracellular Ca2+ content of RBCs was determined using the Ca2+ probe Fluo-3 and flow cytometry. In vivo uptake of Ca2+ ionophore-treated murine RBCs (Ca2+-RBCs) was investigated in recipient mice, using flow cytometry and immunohistochemical analysis.

RESULTS: A small fraction of human RBCs accumulated [Ca2+](i) during storage for up to 42 days under blood bank conditions. In a murine model, where fresh or Ca2+-RBCs were transfused, Ca2+-RBCs were mainly trapped by MARCO+ splenic marginal zone macrophages and CD11c+ CD207+ dendritic cells (DCs) within 1 hour after transfusion. In marked contrast, freshly transfused RBCs aging normally in circulation were cleared much slower and preferentially by F4/80+ red pulp macrophages. CD47 on the Ca2+-RBCs did not affect their clearance by splenic phagocytic cells.

CONCLUSIONS: A small fraction of RBCs accumulate [Ca2+](i) during storage, and in a murine model such RBCs are recognized by splenic macrophages and DCs in ways similar to what has been reported for nucleated apoptotic cells.

National Category
Hematology
Identifiers
urn:nbn:se:umu:diva-125594 (URN)10.1111/trf.13612 (DOI)000380362100025 ()27095001 (PubMedID)
Available from: 2016-09-23 Created: 2016-09-13 Last updated: 2018-06-07Bibliographically approved
Hult, A., Johansson, J., Nordström, P. & Nordström, A. (2016). The importance of bouts of physical activity for type 2 diabetes prevalence. In: Active People, Active Places, Active Policy: Book of Abstracts. Paper presented at The 6th ISPAH International Congress on Physical Activity and Public Health 2016, 16–19 November 2016, Bangkok, Thailand.
Open this publication in new window or tab >>The importance of bouts of physical activity for type 2 diabetes prevalence
2016 (English)In: Active People, Active Places, Active Policy: Book of Abstracts, 2016Conference paper, Oral presentation with published abstract (Other academic)
Abstract [en]

Purpose: The World Health Organization (WHO) suggest that people at least 65 year old should perform 150 min physical activity (PA) per week in bouts of at least 10 minutes. The guidelines are based on predominantly studies with self-reported PA. We evaluated objective measures of PA on T2D prevalence and the WHO guidelines.

Methods: During 2012-2015, a total of 1939 (49% women) individuals, all 70 year old were included in a cross sectional study investigating risk factors for non-communicable diseases; the Healthy Ageing Initiative. Objective measures of PA was attained from accelerometers, worn for one week. T2D was defined by a fasting glucose of ≥7.0 mmol/L or a prior T2D diagnosis.

Results: Based on objectively measured PA, 39% of the studied population reached the minimum requirements for PA as stated by the WHO. Using logistic regression, the odds ratio (OR) for T2D when achieving the WHO recommendations was 0.94 (CI 0.68-1.30). By removing the 10 minute bout prerequisite, the OR decreased to 0.61 (CI 0.45-0.84). Using a cutoff value of 6 000 steps a day further lowered the OR to 0.51 (CI 0.37-0.70), for T2D after adjusting for sex, smoking and amount of visceral fat. Additionally, individuals with no T2D had significantly higher step count as compared with diabetics diagnosed in the study (p<0.05) and prior known T2D diagnosis (p<0.001).

Conclusions: In our investigated cohort, adhering to the WHO guidelines of PA did not reduce the risk for T2D. By discarding the requirement of at least 10 min of consecutive PA, the relative risk was significantly lowered, while the cutoff level of 6 000 steps a day presented the highest risk reduction, demonstrating that every step counts. Notably, individuals with known diabetes had the lowest PA.

Keywords
Physical activity recommendations, Type 2 diabetes mellitus, Objective measures of physical activity
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Research subject
Public health
Identifiers
urn:nbn:se:umu:diva-140689 (URN)
Conference
The 6th ISPAH International Congress on Physical Activity and Public Health 2016, 16–19 November 2016, Bangkok, Thailand
Available from: 2017-10-17 Created: 2017-10-17 Last updated: 2018-09-03Bibliographically approved
Hult, A. (2015). Towards a detailed understanding of the red blood cell storage lesion: and its consequences for in vivo survival following transfusion. (Doctoral dissertation). Umeå: Umeå universitet
Open this publication in new window or tab >>Towards a detailed understanding of the red blood cell storage lesion: and its consequences for in vivo survival following transfusion
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Red blood cells (RBCs) are vital for oxygen delivery to tissues and constitute the vast majority of all cells in blood. After leaving the red bone marrow as mature cells, RBCs have a lifespan of approximately 120 days before they are removed from the circulation by macrophages, mainly in the spleen and liver. RBC transfusion is a common therapy in modern healthcare. Major surgery, numerous cancer treatments and other, often lifesaving, interventions would be unthinkable without available blood supply. For this reason, hospitals store donated RBCs in blood banks.

The metabolic and structural changes that occur during prolonged storage of RBCs (the storage lesion) have been studied in detail in vitro and include oxidative stress, a reduction in glycolysis, increased membrane rigidity and shedding of microparticles from the RBC membrane. Stored RBCs share several features of senescent RBCs, but also with RBCs undergoing an apoptotic-like process called eryptosis. A consequence of the storage lesion is the fact that as much as 25% of stored RBCs could be rapidly removed from the circulation within 24 hours after transfusion. The mechanisms behind this rapid macrophage-mediated recognition and removal of stored RBCs, and its immunological consequences, remain largely unknown. Therefore, the aims of this thesis were to investigate if cryopreserved human RBCs induced an inflammatory response following autologous transfusion into healthy volunteers, and to further understand the mechanisms behind macrophage recognition of stored RBCs in vitro and in vivo.

Autologous transfusion of two units of cryopreserved RBCs into healthy human recipients was found to be associated with an increased extravascular RBC elimination already at 2 hours after transfusion. However, there were no signs of an increased production of any of the investigated pro-inflammatory cytokines, indicating that an increase in the destruction of RBCs per se did not induce an inflammatory response.

Eryptosis is a form of induced RBC death associated with an increased cytoplasmic Ca2+ uptake. We found that a subset of human RBCs increased their Ca2+ permeability during prolonged storage at +4°C. Using a murine model, to further understand how RBCs with an increased Ca2+ permeability were eliminated by phagocytic cells in the spleen, it was found that such RBCs were taken up by marginal zone macrophages and dendritic cells (DCs) in a manner distinct from that of naturally senescent RBCs. The DC population particularly efficient in this process expressed CD207 and are known for their ability to promote immunological tolerance. Eryptotic cell uptake was not regulated by the phagocytosis-inhibitory protein CD47 on the RBCs.

To investigate how RBCs damaged during liquid storage are recognized and taken up by macrophages, a model to store and transfuse murine RBCs was developed. This storage model generated murine RBCs with several characteristics similar to that of stored human RBCs (i.e. loss of ATP, formation of RBC microparticles and rapid clearance of up to 35% of the RBCs during the first 24 h after transfusion). In vitro phagocytosis of human as well as murine stored RBCs was serum dependent and could be inhibited by blocking class A scavenger receptors using fucoidan or dextran sulphate.

In conclusion, the findings of this thesis contribute to further understanding how changes inflicted to RBCs during storage direct the fate of these cells in their interaction with cells of the immune system after transfusion. The observation of an increased Ca2+ permeability of stored RBCs, and the possible recognition of such cells by tolerance-promoting DCs, in combination with the findings that class A scavenger receptors and serum factors may mediate recognition of stored RBCs, may result in novel new directions of research within the field of transfusion medicine.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2015. p. 58
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1727
Keywords
Red blood cell, erythrocyte, transfusion, macrophage, phagocytosis, storage lesion, eryptosis, Class A scavenger receptor
National Category
Cell and Molecular Biology
Research subject
transfusionsmedicin
Identifiers
urn:nbn:se:umu:diva-103270 (URN)978-91-7601-288-8 (ISBN)
Public defence
2015-06-11, Sal BiA 201, Biologihuset, Johan Bures väg 12, Umeå, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2015-05-21 Created: 2015-05-19 Last updated: 2018-06-07Bibliographically approved
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