This project studies the mechanisms of cellular adhesion among subsets of leukocytes and endothelium derived from different tissues. The major hypothesis asks whether adhesion of leukocytes is dependent on organ-specific and activation-specific molecules on the endothelium. An adhesion bioassay is used to screen monoclonal antibodies made against endothelial cultures activated with cytokines. Antisera from mice inoculated with endothelial cultures bind endothelial culture lysates in a tissue-specific fashion as demonstrated by Western blot but as yet, no hybridomas have been identified with the same activity. Preliminary adhesion results show that normal nylon-wool purified leukocytes adhere more aggressively to endothelial monolayers activated with TNF or IL-1 but not with SIV-culture supernatant. Lymphocytes from SIV-infected animals demonstrate similar preferences but are relatively less likely to bind to activated endothelium than lymphocytes from normal animals. Testing of hybridomas and leukocyte adhesion under a variety of clinical and cultural conditions continue. We have shown that supernatant from two clones blocked leukocyte binding to endothelial monolayers. These monoclonal antibodies detected a 84 kDa protein by Western blot and immunoprecipitation. Characterization of these molecules as well as adhesion molecules identified by commercially available antibodies continues.
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