Lymphocyte-derived interferon-gamma mediates ischemia-reperfusion-induced leukocyte and platelet adhesion in intestinal microcirculation.
Although previous studies have implicated lymphocytes in the gut microvascular and inflammatory responses to ischemia-reperfusion (I/R), the lymphocyte population and lymphocyte-derived products that mediate these responses have not been defined. Platelet and leukocyte adhesion was measured in intestinal postcapillary venules of wild-type (WT) mice and mice genetically deficient in either CD4+ T cells (CD4-/-), CD8+ T cells (CD8-/-), B cells (B cell-/-), or interferon-gamma (IFN-gamma-/-) subjected to 45 min of ischemia and 4 h of reperfusion. The I/R-induced platelet and leukocyte recruitment responses were also evaluated following adoptive transfer of WT splenocytes into CD4-/-, CD8-/-, B cell-/-, and IFN-gamma-/- mice. WT mice exposed to gut I/R exhibited significant increases in the adhesion of both platelets and leukocytes, compared with sham-WT mice. These blood cell adhesion responses to I/R were greatly attenuated in CD4-/-, CD8-/-, B cell-/-, and IFN-gamma-/- mice. Adoptive transfer of WT splenocytes restored the WT responses to I/R in all mutants except the B cell-/- mice. These findings implicate both T and B cells and lymphocyte-derived IFN-gamma as mediators of the proinflammatory and prothrombogenic phenotype assumed by intestinal microvessels after I/R.
Osman
Mohammad
M
Department of Molecular and Cellular Physiology, Louisiana State University Health Science Center, 1501 Kings Highway, Shreveport, LA 71130-3932, USA.
Russell
Janice
J
Granger
D Neil
DN
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D001792:Blood Platelets / Q000166:cytology; D001794:Blood Pressure; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology; D006339:Heart Rate; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008833:Microcirculation / Q000276:immunology; D015427:Reperfusion Injury / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014657:Vasculitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D007371:Interferon-gamma