MATRIX PROTEIN-REGULATION OF PMN OXIDATIVE-METABOLISM DURING ISCHEMIA

Matrix proteins upregulate polymorphonuclear neutrophil (PMN) oxidativ e metabolism in a normoxic environment. We sought to investigate the r elationship between matrix proteins and adherent PMN oxidative metabol ism during acute ischemia. PMN adherent to buffer, fibronectin, Arg-Gl y-Asp-Ser (RGDS), or laminin were placed in either normoxic or ischemi c media. PMN adherence, superoxide anion production, (4,5-dimethylthia zol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) formazan production, a nd surface receptor expression (CD64, CD32w, CD16, CD35, and CD11b/CD1 8) using monoclonal antibodies directed against these receptors were a ssayed. Ischemia increased PMN adherence unless the PMN were adhered t o fibronectin or RGDS. Ischemia reduced PMN superoxide anion, MTT form azan, and H2O2 production unless the PMN were adhered to fibronectin o r RGDS. Fibronectin and RGDS prevented ischemic-induced suppression of FcR expression. Immunofluorescent studies demonstrated capping and cl ustering of PMN Fc and complement receptors during ischemia while adhe red on matrix proteins. These results demonstrate that 1) ischemia sup presses matrix protein upregulation of PMN oxidative metabolism, which is restored by fibronectin; 2) fibronectin-mediated restoration of PM N oxidative metabolism involves the binding epitope of fibronectin; an d 3) fibronectin maintains PMN oxidative metabolism during ischemia in part by maintaining PMN FcR on the cell surface and by recruiting a n ew population of PMN capable of undergoing oxidative metabolism.