and specific aims): This is a renewal application for a research program that has addressed mechanisms of oxygen-radical mediated tissue injury, the role of complement in inflammatory injury, and mechanisms of local and remote injury. The past studies have identified a dual role for products of activated neutrophils and complement in upregulating vascular adhesion molecules. They have also demonstrated the ability of complement components to stimulate endothelial cells directly. The proposed studies seek to define the role of C5a and C6 dependent products in lung inflammation using immune complex deposition models or systemic activation of complement (Aim 1). The studies will evaluate how complement activation products regulate expression of vascular ICAM-1 and P-selection (Aim 2) and airway ICAM1 (Aims 3 and 4). The effects of C5a or C5b-9 on pulmonary endothelial cells from a variety of sources will be measured, using assays of neutrophil adhesion, NO production and chemokine production (Aim 5). A thermal injury model will be used to evaluate the role of C5a and C6-dependent products in local and remote organ injury, as part of an effort to understand systemic inflammatory responses (Aim 6).
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