Inhibition of monocyte and polymorphonuclear granulocyte immune phagocytosis by monoclonal antibodies specific for FcγRI, II and III

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 capacity to inhibit monocyte and polymorphonuclear granulocyte (PMN) immune phagocytosis which is mediated by Fc gamma R. We used human red blood cells (rbc) coated with hIgG1 or mIgG1 as Fc gamma RI- and Fc gamma RII-specific target cells, respectively. The Fc gamma RI-specific mAbs 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, CIKM5, FLI8.2, FLI 8.26, 2E1, and 41H16 inhibited Fc gamma RII-specific monocyte immune phagocytosis in all Fc gamma RIIa high-responder (HR) individuals but did not inhibit Fc gamma RI-specific phagocytosis. Using PMN, FL18.2 and 2E1 only partially inhibited phagocytosis in HR individuals, 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 portion binding to Fc gamma RIII and the Fc portion binding to Fc gamma RII.