IgM-mediated opsonization and cytotoxicity in the shark.
Two types of cytotoxic reactions have been observed using cells from the nurse shark: spontaneous cytotoxicity mediated by cells of the macrophage lineage and antibody-dependent killing carried out by a different effector cell population. Previous data showed that removal of phagocytic cells using iron particles abolished macrophage-mediated killing, but not antibody-dependent reactions. The current study used single cell assays and showed that the effector of antibody-driven reactions was the neutrophil. Surprisingly, the mechanism of killing was shown to be phagocytosis mediated by both 7S and 19S immunoglobulin M (IgM). Reactions proceeded with as little as 0.01 microg of purified 19S or 7S IgM and were complete within 4-6 h. In contrast, purified immunoglobulin did not adsorb to macrophages and had no effect on target cell binding or cytotoxicity. Pretreatment of cells with cytochalasin D abolished the phagocytic reaction, but not spontaneous cytotoxicity. These data show that antibody-mediated killing results from opsonization and phagocytosis; the mechanism of macrophage killing is currently unknown. In addition, these data show that the shark neutrophil, not the macrophage lineage, carries a receptor for Fc mu.
McKinney
E C
EC
Department of Microbiology and Immunology, University of Miami School of Medicine, Florida 33101, USA.
Flajnik
M F
MF
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000918:Antibody Specificity; D000920:Antibody-Dependent Cell Cytotoxicity; D007143:Immunoglobulin Heavy Chains / Q000494:pharmacology; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology; D009895:Opsonin Proteins / Q000276:immunology*; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D012754:Sharks / Q000276:immunology*
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D009895:Opsonin Proteins; D011947:Receptors, Antigen, B-Cell