Umeå universitets logga

umu.sePublikationer
Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Assessment of Neutrophil Chemotaxis Upon G-CSF Treatment of Healthy Stem Cell Donors and in Allogeneic Transplant Recipients
Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
Visa övriga samt affilieringar
2018 (Engelska)Ingår i: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 9, artikel-id 1968Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Neutrophils are crucial for the human innate immunity and constitute the majority of leukocytes in circulation. Thus, blood neutrophil counts serve as a measure for the immune system's functionality. Hematological patients often have low neutrophil counts due to disease or chemotherapy. To increase neutrophil counts and thereby preventing infections in high-risk patients, recombinant G-CSF is widely used as adjunct therapy to stimulate the maturation of neutrophils. In addition, G-CSF is utilized to recruit stem cells (SCs) into the peripheral blood of SC donors. Still, the actual functionality of neutrophils resulting from G-CSF treatment remains insufficiently understood. We tested the ex vivo functionality of neutrophils isolated from blood of G-CSF-treated healthy SC donors. We quantified chemotaxis, oxidative burst, and phagocytosis before and after treatment and detected significantly reduced chemotactic activity upon G-CSF treatment. Similarly, in vitro treatment of previously untreated neutrophils with G-CSF led to reduced chemotactic activity. In addition, we revealed that this effect persists in the allogeneic SC recipients up to 4 weeks after neutrophil engraftment. Our data indicates that neutrophil quantity, as a sole measure of immunocompetence in high-risk patients should be considered cautiously as neutrophil functionality might be affected by the primary treatment.

Ort, förlag, år, upplaga, sidor
Frontiers Media S.A., 2018. Vol. 9, artikel-id 1968
Nyckelord [en]
neutrophil, granulocyte colony stimulating factor (G-CSF), allogeneic transplant, chemotaxis, hematopoietic stern cell donor
Nationell ämneskategori
Immunologi inom det medicinska området
Identifikatorer
URN: urn:nbn:se:umu:diva-152255DOI: 10.3389/fimmu.2018.01968ISI: 000444324800001PubMedID: 30254629Scopus ID: 2-s2.0-85053168114OAI: oai:DiVA.org:umu-152255DiVA, id: diva2:1252922
Forskningsfinansiär
Västerbottens läns landstingTillgänglig från: 2018-10-03 Skapad: 2018-10-03 Senast uppdaterad: 2025-01-15Bibliografiskt granskad
Ingår i avhandling
1. Neutrophils in cancer and cancer treatment
Öppna denna publikation i ny flik eller fönster >>Neutrophils in cancer and cancer treatment
2025 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Alternativ titel[sv]
Neutrofiler vid cancer och cancerbehandling
Abstract [en]

As part of innate immunity, neutrophils constitute the first line of defense against microbial infections. A low neutrophil count is a considerable risk factor for acquiring severe infections and is a common side effect for patients undergoing chemotherapy. Whether or not neutrophil function is affected by chemotherapy is still largely unknown. We evaluated the functions of neutrophils derived from the newly generated bone marrow of patients who underwent allogeneic stem cell transplantation. We sought to understand whether extended neutrophil dysfunction could add to the risk of infection. For this purpose, we assessed chemotaxis, phagocytosis, and oxidative burst using fluorescence- and luminol-based methods in neutrophils from transplanted patients. We found a decrease in chemotactic ability two weeks after neutrophil engraftment, and the lowered response only normalized at later time points. Interestingly, we observed a similar reduction in chemotactic ability in neutrophils isolated from healthy stem cell donors undergoing treatment with granulocyte-colony-stimulating factor (G-CSF) to prepare for stem cell donation, suggesting that this effect might be transferred to the newly generated neutrophils by an unknown mechanism.

Chemotherapy-free treatment against acute promyelocytic leukemia (APL) using arsenic in combination with retinoic acid has proven to be effective. One of the additional benefits is a decreased risk of neutropenia; however, to what extent the treatment affects neutrophil function remains unknown. We found that neutrophil function was altered in a compensatory manner, with increased chemotaxis at time points with decreased numbers of neutrophils.

In solid cancers, a high number of neutrophils in peripheral blood is often linked to a worse prognosis. In these instances, neutrophils frequently accumulate in the tumor microenvironment. We used a co-culture model with breast cancer cells and stromal cells to investigate the interaction between neutrophils and the tumor microenvironment. Culturing the cells together created a proinflammatory environment, much like the scenario seen in cancerous tissue. The supernatant was chemoattractive to neutrophils from healthy donors and activated them to produce reactive oxygen species. When neutrophils were added to the co-culture model, using Seahorse analysis, we observed a shift in the metabolic pattern of the co-culture, creating an increase in mitochondrial function. We conclude that the increased mitochondrial activity indicates a protumorigenic effect exerted by neutrophils.In summary, neutrophil function in patients with hematological diseases is altered due to treatment and could contribute to patients' susceptibility to infection. Neutrophils alter the metabolism of cells in a cancer fibroblast co-culture, favoring the tumor cells, suggesting that neutrophils might be a promising target for future anticancer treatment.

Ort, förlag, år, upplaga, sidor
Umeå: Umeå University, 2025. s. 64
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 2342
Nyckelord
neutrophil, chemotaxis, tumor microenvironment, tumor cell metabolism, cancer, G-CSF, allogeneic transplantation, acute promyelocytic leukemia
Nationell ämneskategori
Hematologi
Forskningsämne
immunologi
Identifikatorer
urn:nbn:se:umu:diva-234107 (URN)978-91-8070-592-9 (ISBN)978-91-8070-593-6 (ISBN)
Disputation
2025-02-14, Hörsal D, by 1D, plan 9, Umeå Universitetssjukhus, Umeå, 09:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2025-01-24 Skapad: 2025-01-15 Senast uppdaterad: 2025-01-16Bibliografiskt granskad

Open Access i DiVA

fulltext(3450 kB)318 nedladdningar
Filinformation
Filnamn FULLTEXT01.pdfFilstorlek 3450 kBChecksumma SHA-512
a3d90ee576f4a8a999a5c80f233678650438d92b0583b73946f40cb64f2e3888315c0d5db0edded0480cd221b9ac5420f1ca6a7a67b4377d1ad829a9ed205115
Typ fulltextMimetyp application/pdf

Övriga länkar

Förlagets fulltextPubMedScopus

Person

Thunström Salzer, AnnaNiemiec, Maria JoannaHosseinzadeh, AvaStylianou, MariosRöhm, MarcAhlm, ClasWahlin, AndersErmert, DavidUrban, Constantin F.

Sök vidare i DiVA

Av författaren/redaktören
Thunström Salzer, AnnaNiemiec, Maria JoannaHosseinzadeh, AvaStylianou, MariosRöhm, MarcAhlm, ClasWahlin, AndersErmert, DavidUrban, Constantin F.
Av organisationen
OnkologiInstitutionen för klinisk mikrobiologiMolekylär Infektionsmedicin, Sverige (MIMS)
I samma tidskrift
Frontiers in Immunology
Immunologi inom det medicinska området

Sök vidare utanför DiVA

GoogleGoogle Scholar
Totalt: 318 nedladdningar
Antalet nedladdningar är summan av nedladdningar för alla fulltexter. Det kan inkludera t.ex tidigare versioner som nu inte längre är tillgängliga.

doi
pubmed
urn-nbn

Altmetricpoäng

doi
pubmed
urn-nbn
Totalt: 634 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf