ENDOTOXIN-INDUCED, NEUTROPHIL-MEDIATED ENDOTHELIAL CYTOTOXICITY IS ENHANCED BY T-LYMPHOCYTES

The role of T-lymphocytes (T cells) and interferon-gamma (IFN-gamma) i n the pathogenesis of sepsis-induced microvascular endothelial injury remains unclear, We sought to determine whether the syngeneic cocultur e of human T cells in the presence of LPS promoted subsequent neutroph il (PMN)-mediated endothelial cytotoxicity, Syngeneic T cells were coc ultured with Cr-51-loaded human adipose microvascular endothelial cell (HAMVEC) monolayers in the absence and presence of LPS. Subsequent PM N-mediated HAMVEC cytotoxicity (measured as percent specific Cr-51 rel ease) was absent in cultures that contained T cells but no LPS and was significantly increased when T cells were cocultured in the presence of LPS, This was true both following addition of unstimulated PMNs (-0 .8 +/- 3.0% vs 4.9 +/- 4.7% for T cells alone vs T cells plus LPS, res pectively) and PMNs stimulated with f-Met-Leu-Phe (-0.4 +/- 3.1% vs 10 .7 +/- 3.0% for T cells alone vs T cells plus LPS, respectively), Incr eased cytotoxicity was associated with increased expression of the end othelial adhesion molecules ICAM-1 and VCAM-1. Control experiments fai led to demonstrate cytotoxicity when HAMVEC were cultured in the prese nce of IFN-gamma alone, LPS alone, or T cells without LPS, It appears that there is a necessary requirement of both LPS and (presumably acti vated) T cells or their products (other than IFN-gamma) for enhanced P MN-mediated endothelial cytotoxicity, This phenomenon may also be medi ated by increased expression of endothelial adhesion molecules that pr omote subsequent PMN adhesion, (C) 1997 Academic Press.