Hypoxia induces an opsonic mismatch on the polymorphonuclear leukocyte surface-reversal via Arg-Gly-Asp-Ser-mediated adhesion.
Hypoxia remains an important clinical problem and affects neutrophil oxygen-dependent microbicidal pathways. For adequate PMN-cidal activity to occur, two sets of opsonic receptors (FcR, CD16, CD32w; complement receptors, CD35, CD11b/CD18) must be expressed on the cell surface. We hypothesized that hypoxia would adversely affect receptor expression and that the biological surface that the PMN were adhered to would modulate the effect of hypoxia on these receptors. PMN were adhered in the presence of buffer, fibronectin, Arg-Gly-Asp-Ser (RGDS), or laminin followed by assessment of PMN FcR and complement receptors using 125I-labeled monoclonal antibodies directed against these receptors. Hypoxia reduced PMN CD16 and CD32w but not CD35 and CD11b/CD18 expression. Decreasing buffer pO2 led to corresponding decreases in CD16 and CD32w expression. RGDS but not fibronectin or laminin restored CD16 and CD32w expression in the presence of hypoxia. Monensin but not cycloheximide inhibited RGDS restoration of CD16 and CD32w. (cpm bound: CD16, 958 +/- 123 vs 1602 +/- 193; CD32w, 1481 +/- 173 vs 2215 +/- 382 for hypoxia buffer+RGDS +/- monensin.) These results demonstrate that: (1) acute hypoxia creates an opsonic mismatch by reducing CD16 and CD32w without affecting complement receptors CR1 and CR3 (CD35, CD11b/CD18); (2) matrix proteins modulate the effect of acute hypoxia on PMN FcR; (3) the RGDS-binding epitope of fibronectin significantly restores PMN FcR in the face of acute hypoxia; and (4) RGDS upregulates FcR expression during acute hypoxia by increasing receptor recycling to the cell surface.
Department of Surgery, Brown University School of Medicine/Rhode Island Hospital, Providence 02903.
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D002448:Cell Adhesion; D006801:Humans; D000860:Hypoxia / Q000473:pathology / Q000503:physiopathology*; D009504:Neutrophils / Q000502:physiology*; D009842:Oligopeptides / Q000502:physiology*; D009895:Opsonin Proteins / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D010313:Partial Pressure; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011961:Receptors, Fc / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism
D009842:Oligopeptides; D009895:Opsonin Proteins; D011956:Receptors, Cell Surface; D011961:Receptors, Fc; D017452:Receptors, IgG; C046617:arginyl-glycyl-aspartyl-serine; D010100:Oxygen