In previous grant periods, we have found that egg albumin-induced anaphylaxis in guinea pigs is characterized in part by extensive occlusion of the pulmonary microvascular bed. For the proposed project, our major objective is to help define the sequence of events set in course during the first few min of anaphylaxis that lead to microvascular occlusion. The project is subdivided into two subprojects aimed at answering the following questions: 1. Can assays of endothelial surface enzymes, in vivo, be used to evaluate severity, and then progression or remission, of the lung microvascular injury of aggregate anaphylaxis? 2. Can pulmonary endothelial cells in culture be used to replicate events that lead to loss of microvascular integrity? Success in answering question 1. may provide minimally-invasive methods for evaluating severity and progression of pulmonary microvascular occlusion at the bedside, not only for patients with anaphylactoid reactions but also for those with other forms of the adult respiratory distress syndrom. Success in subproject 2. should provide clearer understanding of how pulmonary endothelium is damaged and insights into how it might be protected.
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