AJP - Cell Physiology, Vol 266, Issue 3 C637-C647, Copyright © 1994 by American Physiological Society
Matrix protein regulation of PMN oxidative metabolism during ischemia
H. Simms and R. D'Amica
Department of Surgery, Brown University School of Medicine/Rhode Island Hospital, Providence 02903.
Matrix proteins upregulate polymorphonuclear neutrophil (PMN) oxidative
metabolism in a normoxic environment. We sought to investigate the
relationship between matrix proteins and adherent PMN oxidative metabolism
during acute ischemia. PMN adherent to buffer, fibronectin, Arg-Gly-Asp-Ser
(RGDS), or laminin were placed in either normoxic or ischemic media. PMN
adherence, superoxide anion production,
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) formazan
production, and surface receptor expression (CD64, CD32w, CD16, CD35, and
CD11b/CD18) using monoclonal antibodies directed against these receptors
were assayed. Ischemia increased PMN adherence unless the PMN were adhered
to fibronectin or RGDS. Ischemia reduced PMN superoxide anion, MTT
formazan, and H2O2 production unless the PMN were adhered to fibronectin or
RGDS. Fibronectin and RGDS prevented ischemic-induced suppression of FcR
expression. Immunofluorescent studies demonstrated capping and clustering
of PMN Fc and complement receptors during ischemia while adhered on matrix
proteins. These results demonstrate that 1) ischemia suppresses matrix
protein upregulation of PMN oxidative metabolism, which is restored by
fibronectin; 2) fibronectin-mediated restoration of PMN oxidative
metabolism involves the binding epitope of fibronectin; and 3) fibronectin
maintains PMN oxidative metabolism during ischemia in part by maintaining
PMN FcR on the cell surface and by recruiting a new population of PMN
capable of undergoing oxidative metabolism.
