MECHANISMS OF NEUTROPHIL ADHERENCE

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Adherence of neutrophils to endothelial cells represents a necessary step in the emigration of neutrophils to inflammatory sites. In contrast to augmentation of natural host defense to infection, the intensified adhesiveness and aggregation of neutrophils noted with hemodialysis leukopenia has been suggested to result in the development of acute lung injury by virtue of increased sequestration and subsequent damage to endothelium. Similar mechanisms of injury involving neutrophils have been implicated in the Adult Respiratory Distress Syndrome (ARDS), immune complex diseases and in acute myocardial infarction. The objective of the proposed research is to determine mechanisms by which human neutrophils adhere to vascular surfaces. The proposed studies will involve purification and characterization of cell-surface proteins involved in adherence of neutrophils to surfaces including cultured human endothelial cells. The role of naturally occurring noncomplement derived serum factors and endothelial cell factors in modulating secretagogue induced neutrophil adherence will also be determined. Furthermore, experiments will be performed to determine whether adherence of neutrophils to surfaces results in rearrangement of cytoskeletal structures. These studies should yield new information regarding mechanisms of neutrophil adherence to endothelial cells thought to be important in the pathogenesis of many neutrophil-mediated vascular diseases, such as ARDS and diseases in which neutrophil activated may play a pathogenetic role. They may also provide clues to more rational forms of therapy.