Fc gamma receptor III induces actin polymerization in human neutrophils and primes phagocytosis mediated by Fc gamma receptor II.
Human polymorphonuclear leukocytes (PMN) express two classes of Fc gamma R: Fc gamma RII the 42-kDa receptor with a traditional membrane spanning domain and cytoplasmic tail and Fc gamma RIIIPMN the 50- to 80-kDa receptor with a glycosyl-phatidylinositol membrane anchor expressed on PMN. To explore the capacity of Fc gamma RIIIPMN to generate intracellular signals, we have analyzed the ability of Fab and F(ab')2 anti-Fc gamma R mAb to induce actin filament assembly, a prerequisite for motile behaviors. Multivalent ligation of Fc gamma RIIIPMN, independent of Fc gamma RII, results in an increase in F-actin content that is [Ca2+]i dependent. Multivalent ligation of Fc gamma RII also initiates actin polymerization but uses a [Ca2+]i-independent initial pathway. In addition to providing a mechanism for Fc gamma RIIIPMN triggered effector functions, the increase in F-actin and [Ca2+]i generated by Fc gamma RIIIPMN ligation also serves as a "priming" signal to modify PMN responses to other stimuli. Experiments using erythrocytes specifically coated with anti-Fc gamma RII Fab demonstrate that cross-linking of Fc gamma RIIIPMN with anti-Fc gamma RIII F(ab')2 enhances phagocytosis mediated by Fc gamma RII. Thus, Fc gamma RIIIPMN, a glycosyl-phosphatidylinositol anchored protein, may contribute directly to an intracellular program of actin assembly that may trigger and prime neutrophil effector functions.
Salmon
J E
JE
Hospital for Special Surgery, Cornell University Medical College, New York, NY 10021.
Brogle
N L
NL
Edberg
J C
JC
Kimberly
R P
RP
D000199:Actins / Q000032:analysis / Q000378:metabolism*; D000936:Antigen-Antibody Complex / Q000502:physiology; D000943:Antigens, Differentiation / Q000502:physiology*; D002118:Calcium / Q000502:physiology; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism*; D010587:Phagocytosis; D011108:Polymers / Q000378:metabolism; D011961:Receptors, Fc / Q000502:physiology*; D017452:Receptors, IgG; D015398:Signal Transduction
D000199:Actins; D000936:Antigen-Antibody Complex; D000943:Antigens, Differentiation; D007074:Immunoglobulin G; D011108:Polymers; D011961:Receptors, Fc; D017452:Receptors, IgG; D002118:Calcium