FcR-independent antibody-mediated cellular cytotoxicity.
In this study we used palmitate-derivatized antibodies (pal-Ab) to examine the minimum contribution of Fc receptors (FcR) to macrophage (M phi)-mediated lysis and phagocytosis in antibody-dependent cellular cytotoxicity (ADCC). Pal-Ab specific for chicken erythrocytes (CE) were incorporated into the plasma membranes of M phi by insertion of the palmitate hydrocarbon chains into the outer leaflet of the phospholipid bilayer. In this system, the palmitate anchor bypassed the requirement for FcR in antibody-dependent effector-target conjugation and provided a unique opportunity to uncouple antibody-FcR interactions in ADCC. We show that binding of CE targets by P388D1 M phi effector cells through anti-CE pal-F(ab')2 can lead to efficient extracellular target cell lysis, but not phagocytosis. In contrast, pal-F(ab')2-mediated interactions between CE and peritoneal exudate M phi (PEM) activated both ingestion and extracellular lysis of the targets. In normal ADCC, FcR-dependent interactions between CE and either P388D1 cells or PEM triggered both extracellular lysis and phagocytosis. Our results demonstrate that lysis and phagocytosis in CE-directed ADCC by M phi have different minimum requirements for FcR functions. Moreover, our results suggest that FcR-independent triggers on the PEM surface are capable of triggering target cell lysis and internalization following antibody-mediated interactions.
Colsky
A S
AS
Department of Microbiology and Immunology, University of Miami School of Medicine, Florida 33101.
Mendez
L E
LE
Peacock
J S
JS
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002645:Chickens; D004912:Erythrocytes / Q000276:immunology / Q000502:physiology / Q000648:ultrastructure; D007141:Immunoglobulin Fc Fragments / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D008264:Macrophages / Q000276:immunology / Q000502:physiology* / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D010168:Palmitates / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000502:physiology; D011961:Receptors, Fc / Q000276:immunology / Q000502:physiology*
D000906:Antibodies; D007141:Immunoglobulin Fc Fragments; D010168:Palmitates; D011961:Receptors, Fc