INVOLVEMENT OF THE PERTUSSIS-TOXIN-SENSITIVE GTP-BINDING PROTEIN IN REGULATION OF EXPRESSION AND FUNCTION OF GRANULOCYTE COMPLEMENT RECEPTOR TYPE-1 AND TYPE-3

Human polymorphonuclear leukocytes (PMN) express receptors for complem ent (C) C3b and C3bi termed CR1 and CR3, respectively. The addition of PMA or fMLP to PMN enhances the capacity of these receptors to promot e binding of C3b- and C3bi-coated erythrocytes. fMLP-depen dent increa se of the binding of these ligand-coated erythrocytes was completely a bolished by prior exposure of the PMN to pertussis toxin (IAP). GTP-bi nding protein (Gi alpha) was ADP-ribosylated and dysfunctional by this treatment. On the other hand, PMA-dependent binding of these ligands, as well as control binding, was inhibited only slightly, if at all, b y the IAP treatment. The levels of C receptor expression on cell surfa ce were determined by flow cytometry using monoclonal antibody against CR1 and those against the alpha and beta chains of CR3 (CR3 is compos ed of alpha and beta chain). Upon exposure of PMN to the chemotactic f actor or PMA, or upon incubation of the cells at 37 degrees C, the sur face expression of CR1 and CR3 alpha was increased. IAP also blocked a n fMLP-induced increase of CR1 and CR3 alpha, but did not block the te mperature- or PMA-dependent increase of these receptors. Opsonized zym osan (SOZ), another ligand for CR3, also led to an increase of both CR 1 and CR3 alpha. Neither PMA nor SOZ brought about an increase of the surface expression of CR3 beta, but fMLP caused a slight increase of C R3 beta in an IAP-sensitive manner. Based on the IAP-sensitivity of th e receptor expression, therefore, it appears that at least two separat e mechanisms are operative in the control of C receptors. In addition, the alpha and beta chains of CR3 are regulated independently. The pre sent data offer evidence suggesting that C receptor functions are in p art regulated through a GTP-binding protein via modulation of their su rface expression.