Phagocytosis occurs in vivo primarily by polymorphonuclear leukocytes and mononuclear phagocytes adherent to tissue surfaces such as the vascular endothelium, basement membranes and the extracellular matrix surrounding areas of inflammation and tissue injury. Recent studies have demonstrated the importance of surface contact in regulating phagocyte functional activities, although much less is known regarding alterations in phagocyte metabolism and secretion which occurs following adherence to such tissue surfaces. Modulation of mononuclear phagocyte secretion of arachidonic acid products has been proposed as and important immunoregulatory mechanism of phagocyte activity. In view of the fact that the peripheral blood mononuclear phagocyte, i.e. the monocyte, differentiates into inflammatory and activated macrophages in response to various signals and cytokines during their contact and migration through tissue surfaces, we hypothesize that arachidonic acid products released by mononuclear phagocytes during surface contact will be of importance in regulating macrophage activities. The proposed studies will be divided into two major parts: 1) to investigate the phagocytic and cytotoxic activities of mononuclear phagocytes adherent to the extracellular matrix and various protein components of the matrix; 2) to measure changes in arachidonic acid metabolites released from mononuclear phagocytes during adherence to matrix protein surfaces and determine whether these metabolites are an important feedback mechanism regulating phagocytic and cytotoxic activities. The results of these proposed studies will provide not only new information on how the extracellular matrix proteins modulate phagocytic activity, but also new insights into the regulation of phagocyte function and secretin at sites of tissue injury.
| Odekon, L E; Gilboa, N; Del Vecchio, P et al. (1992) Urokinase in conditioned medium from phorbol ester-pretreated endothelial cells promotes polymorphonuclear leukocyte migration. Circ Shock 37:169-75 |
| Gudewicz, P W; Frewin, M B (1991) Surface contact modulation of inflammatory macrophage antibody dependent cytotoxicity and prostanoid release. J Cell Physiol 149:195-201 |
| Daudi, I; Gudewicz, P W; Saba, T M et al. (1991) Proteolysis of gelatin-bound fibronectin by activated leukocytes: a role for leukocyte elastase. J Leukoc Biol 50:331-40 |
