INHIBITION OF MONOCYTE AND POLYMORPHONUCLEAR GRANULOCYTE IMMUNE PHAGOCYTOSIS BY MONOCLONAL-ANTIBODIES SPECIFIC FOR FC-GAMMA-RI, FC-GAMMA-RII AND FC-GAMMA-RIII

We tested two Fc gamma receptor I (Fc gamma RI); six Fc gamma RII; and six Fc gamma RIII-specific monoclonal antibodies (mAb) for their capa citiy to inhibit monocyte and polymorphonuclear granulocyte (PMN) immu ne phagocytosis which is mediated by Fc gamma R. We used human red blo od cells (rbc) coated with hIgG1 or mIgG1 as Fc gamma RI- and Fc gamma RII-specific target cells, respectively. The Fc gamma RI-specific mAb s 22.2 and 32.2 did not inhibit Fc gamma RI- or Fc gamma RII-specific monocyte immune phagocytosis. The Fc gamma RII-specific mAbs IV.3, CIK M5, FLI8.2, FLI 8.26, 2E1, and 41H16 inhibited Fc gamma RII-specific m onocyte immune phagocytosis in all Fc gamma RIIa high-responder (HR) i ndividuals but did not inhibit Fc gamma RI-specific phagocytosis. Usin g PMN, FLI8.2 and 2E1 only partially inhibited phagocytosis in HR indi viduals, but the Fc gamma RIII-specific mAbs 3G8, DJ130c, MFM-154, B88 -9 and MG38 completely inhibited Fc gamma RII-specific phagocytosis if the corresponding antigen was available on the cell surface. In these cases phagocytosis inhibition may be explained by cross-linking of Fc gamma RII and Fc gamma RIII via one antibody molecule, with the Fab p ortion binding to Fc gamma RIII and the Fc portion binding to Fc gamma RII.