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INFLAMMATION/IMMUNITY/MEDIATORS

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

Department of Molecular and Cellular Physiology, Louisiana State University Health Science Center, Shreveport, Louisiana

Submitted 14 August 2008 ; accepted in final form 26 December 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- (IFN-^–/–) 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-^–/– 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-^–/– 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- as mediators of the proinflammatory and prothrombogenic phenotype assumed by intestinal microvessels after I/R.

inflammation; microcirculation; cytokine; platelet-leukocyte adhesion