Soluble and surface-bound immunoglobulin triggers human monocyte activation and hydrogen peroxide release.
Human mononuclear phagocytes (MO) can mediate the destruction of a variety of foreign and tumor target cells. In most circumstances, however, peripheral blood MO are noncytotoxic and must acquire cytotoxic activity. To investigate the cell surface molecules that participate in the acquisition of MO-mediated cytotoxicity, we used a panel of monoclonal antibodies (MAbs) recognizing a variety of membrane molecules. MAbs to eight different MO surface molecules did not trigger the killing of tumor target cells. To determine if these cell surface molecules triggered an activated but incomplete lytic mechanism, the ability of these molecules to trigger hydrogen peroxide (H2O2) release was assessed. Several MAbs triggered H2O2 release from MO isolated from the peripheral blood. The pattern of MAb-triggered H2O2 release correlated not with the MO surface antigen, but with the immunoglobulin (Ig) isotype. Isotype-specific H2O2 release was abrogated with the enzymatic removal of the Fc portion of the Ig and enhanced by interferon-gamma pretreatment, indicating that the membrane signal was mediated by cell surface Fc receptors. H2O2 release was independent of the presentation of the Ig molecule. Comparable H2O2 release was observed whether the Ig was in surface-bound or soluble form. These data support an important role for Fc receptors in the acquisition of cytotoxic potential by human MO.
Mentzer
S J
SJ
Division of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115.
Faller
D V
DV
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000502:physiology; D015214:Antigens, Differentiation, Myelomonocytic / Q000502:physiology; D000954:Antigens, Surface / Q000502:physiology; D018821:CD18 Antigens; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000502:physiology; D007132:Immunoglobulin Isotypes / Q000502:physiology; D066298:In Vitro Techniques; D009000:Monocytes / Q000276:immunology*; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D011971:Receptors, Immunologic / Q000502:physiology*; D016028:Receptors, Leukocyte-Adhesion / Q000502:physiology; D015398:Signal Transduction; D012995:Solubility
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000954:Antigens, Surface; D018821:CD18 Antigens; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D011947:Receptors, Antigen, B-Cell; D011971:Receptors, Immunologic; D016028:Receptors, Leukocyte-Adhesion; D006861:Hydrogen Peroxide