Submitted on August 14, 2008
Revised on December 15, 2008
Accepted on December 26, 2008
Lymphocyte-derived interferon-
mediates ischemia-reperfusion induced leukocyte and platelet adhesion in intestinal microcirculation
Mohammad Osman1, Janice M. Russell1, and D. Neil Granger1*
1 Louisiana State University Health Sciences Center
* To whom correspondence should be addressed. E-mail: dgrang{at}lsuhsc.edu.
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 hrs 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 to 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 pro-inflammatory and prothrombogenic phenotype assumed by intestinal microvessels after I/R.
