umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Expression of carcinoembryonic antigen and nonspecific cross-reacting 50-kDa antigen in human normal and cancerous colon mucosa: comparative ultrastructural study with monoclonal antibodies
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
1994 (English)In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 54, no 12, 3305-3314 p.Article in journal (Refereed) Published
Abstract [en]

The precise localization of carcinoembryonic antigen (CEA) and non-specific cross-reacting 50-kDa antigen (NCA 50) in normal colon mucosa and colon adenocarcinoma was investigated by using an indirect immunoperoxidase electron microscopic technique with specific monoclonal antibodies. In normal adult colon both antigens were localized to microvesicles and filaments of the "fuzzy coat" on the apical surface of the epithelial cells. In addition, NCA 50 was found in the narrow spaces between adjoining microvilli. Mature columnar cells at the free luminal surface contained most of the antigen positive material. CEA and NCA 50 were also detected as intracellular components of goblet cells. In multilayered tumor glands, the cell surface expression of the antigens was dependent on the position of the tumor cell in the gland. The neoplastic cells showed either a predominant apical labeling or a positive staining of almost the entire cell surface. Some of the neoplastic cells contained CEA in so-called "intracellular lumina." In contrast to normal colon epithelial cells most tumor cells synthesized NCA 50 actively. In normal colonic mucosa, unlike in cancerous tissue, CEA and NCA 50 appear to be released via vesicles formed from the microvillous membrane of mature columnar cells. These results are consistent with the hypothesis that CEA and NCA play a role in the nonspecific defense against microorganisms in the large intestine.

Place, publisher, year, edition, pages
1994. Vol. 54, no 12, 3305-3314 p.
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:umu:diva-73381PubMedID: 8205554OAI: oai:DiVA.org:umu-73381DiVA: diva2:631225
Available from: 2013-06-20 Created: 2013-06-20 Last updated: 2017-12-06Bibliographically approved
In thesis
1. Specific and nonspecific immune mechanisms in human gut: a comparative study of normal and ulcerative colitis intestine
Open this publication in new window or tab >>Specific and nonspecific immune mechanisms in human gut: a comparative study of normal and ulcerative colitis intestine
1996 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The intestine, with its large mucosal surface area, digests and absorbs food nutrients and maintains a beneficial microbial flora in the colon. Local protective immune responses against intestinal pathogens ensure the survival of the individual. These immune reactions are both specific and non-specific in nature. The intestinal epithelium is single-layered and constantly renewed with differentiating epithelial cells moving from the crypt to the luminal surface. Intraepithelial lymphocytes (IEL) are interspersed between the epithelial cells. Ulcerative colitis (UC) is a life-threatening chronic inflammation affecting colon.

In this study three molecules belonging to the carcinoembryonic antigen (CEA) family, namely CEA proper, nonspecific cross-reacting antigen 50/90 (NCA 50/90) and biliary glycoprotein (BGP), were found to be specifically localized to the apical surface of colonic epithelial cells. Full expression of these molecules occurs when the cells reach the upper 1/3 of the crypts and are maintained on the mature cells at the luminal surface. Ultrastructurally, CEA, NCA50/90 and BGP are localized to microvesicles and microfilaments of the fuzzy coat/glycocalyx as well as to the microvilli of the epithelial cells. Their unique localization and documented bacterial binding capacities suggest that they have a role in innate immunity.

Functional analysis of IEL in normal jejunum, ileum and colon revealed that IEL are in vivo activated T-lymphocytes expressing mRNA for the cytokines IL-1β, IL-2, IL-8, IFNγ and TNFα and that jejunal IEL have T-cell receptor (TCR)/CD3 dependent cytolytic capacity. As many as 10% of IEL actively produce IFNγ. CD4+TCRαβ+IEL, CD8+TCRαβ+IEL and CD4-CD8-TCRαβ+IEL all had a TH1/cytotoxic cytokine profile. IEL could be further stimulated in vitro to express IL-10, TNFβ and TGFβ1, to proliferate and to secrete IFNγ. Thus, active protection and/or regulation of the epithelium via cell-mediated immune reactions are prominent in the gut.

UC colon was characterized by a marked lymphocyte infiltration in the lamina propria, 10-50 times the normal level. Most lymphocytes were present in follicle-like cell aggregates containing both T- and B-cells. An unexpected finding was that γδT-cells constituted about 15% of the cells in the aggregates. Such cells are only found intraepithelially in normal gut. γδT-cells of both the intestinal- (TCR-Vδ1/Vγ8) and blood type (TCR-Vδ2/Vγ9) were seen. T-cells in UC colon were activated but nonproliferating and had a down-regulated TCR/CD3 complex. RT-PCR and quantitative immunohistochemistry for cytokine mRNA (n=11) and protein respectively, revealed that the T-cells in UC colon did not produce IL-2, in marked contrast to T-cells in normal colon and to ileal T-cells from UC patients. This was a selective defect since TNFα, IFNγ, IL-1β, IL-8 and TGFβ1 were similarly expressed in normal colon. No TH2 cytokines were seen. Lamina propria leukocytes in UC colon expressed IL-6, a cytokine not found in normal colon. The epithelial cells of UC colon were activated expressing MHC class II antigens, heat shock proteins and the co-stimulatory molecule B7.1/CD80.

Our study demonstrates that UC is an immunological disease. The immunopathological picture seen in UC colon probably reflects an inappropriate down-regulation of local immune responses perhaps due to a selective loss of the key cytokine IL-2 in a situation of extreme antigenic stress.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 1996. 95 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 485
Keyword
human intestine, ulcerative colitis, lymphoid aggregates, intraepithelial lymphocytes, lamina propria lymphocytes, γδT-cells, cytokines, IL-2, carcinoembryonic antigen, biliary glycoprotein, epithelial cells, glycocalyx
National Category
Cancer and Oncology Gastroenterology and Hepatology
Identifiers
urn:nbn:se:umu:diva-73387 (URN)91-7191-235-5 (ISBN)
Public defence
1996-11-08, Astrid Fagraeussalen (A103), Norrlands universitetssjukhus, Umeå, 10:00
Opponent
Supervisors
Available from: 2013-06-20 Created: 2013-06-20 Last updated: 2013-06-20Bibliographically approved

Open Access in DiVA

No full text

PubMed

Search in DiVA

By author/editor
Yeung, Moorix Mo-WaiHammarström, Sten
By organisation
Immunology/Immunchemistry
In the same journal
Cancer Research
Cancer and Oncology

Search outside of DiVA

GoogleGoogle Scholar

pubmed
urn-nbn

Altmetric score

pubmed
urn-nbn
Total: 112 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf