American journal of physiology. Gastrointestinal and liver physiology
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Am. J. Physiol. Gastrointest. Liver Physiol. · Mar 2009
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. ⋯ 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.