Lymphocyte-derived interferon-γ mediates ischemia-reperfusion-induced leukocyte and platelet adhesion in intestinal microcirculation

Osman M, Russell J, Granger DN. Lymphocyte-derived interferon-gamma mediates ischemia-reperfusion-induced leukocyte and platelet adhesion in intestinal microcirculation. Am J Physiol Gastrointest Liver Physiol 296: G659-G663, 2009. First published December 31, 2008; doi:10.1152/ajpgi.90495.2008.-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 cel(-/-), 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.