Adhesion of rheumatoid lymphocytes to mucosal endothelium: the gut revisited.
By a study of the adhesion of rheumatoid mononuclear cells, we have sought to clarify the homing properties and origins of cells likely to be involved in the pathogenesis of this disease. The adhesion of mononuclear cells from patients with rheumatoid arthritis (RA) was enumerated by an in vitro adherence assay using frozen sections of endothelium-containing gut lamina propria (EGLP) from porcine small intestine. Preliminary studies verified the involvement of known adhesion molecules by inhibition assays using monoclonal antibodies Meca-367, Mel-14 and Hermes-3. Twenty-five paired samples of peripheral blood (PB) and synovial fluid (SF) were studied, plus six from synovial membrane (SM) and eight from patients with other diseases. There was a significantly greater degree of adherence to EGLP by SF cells than PB (mean adherence 266 +/- 22 cells/mm(2), compared to 136 +/- 13 cells/mm(2), respectively, the majority of which were CD8+ cells; P=0.02, Mann-Whitney U-test for 25 paired samples). The results of the monoclonal antibody inhibition assays were in keeping with the involvement of homing receptors to gut endothelium in our assay system. Synovial fluid lymphocytes from RA patients exhibited adhesion properties more in keeping with lymphocytes of mucosal than of lymph node origin. Synovial membrance lymphocytes, by contrast, showed poor adherence to endothelium-containing lamina propria. The gut, as an immune lymphoid organ, may thus play a contributory role in this disease, possibly through the pathological seeding of cells into the synovial space.
Kadioglu
A
A
Department of Microbiology & Immunology, University of Leicester, UK.
Sheldon
P
P
D000818:Animals; D000911:Antibodies, Monoclonal; D001172:Arthritis, Rheumatoid / Q000473:pathology* / Q000503:physiopathology; D002448:Cell Adhesion; D004848:Epithelium / Q000502:physiology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000502:physiology; D016131:Lymphocyte Subsets / Q000502:physiology; D008214:Lymphocytes / Q000502:physiology*; D008297:Male; D013552:Swine; D013582:Synovial Fluid / Q000502:physiology
D000911:Antibodies, Monoclonal