The low affinity Fc gamma RIIa and Fc gamma RIIIb on polymorphonuclear neutrophils are differentially regulated by CD45 phosphatase.
Stimulation of human polymorphonuclear neutrophils through ligation and cross-linking of the low affinity Fc gamma RIIa and Fc gamma RIIIb using mAb Fab and F(ab')2 fragments led to transient intracellular calcium mobilization and activation of the respiratory burst. Fc gamma RIIIb engagement resulted in a different pattern of intracellular calcium flux, and induction of the respiratory burst was significantly more effective than in the case of Fc gamma RIIa. These data demonstrate that the capacity of Fc gamma RIIIb to transduce transmembrane signals itself contributes to full cell activation. Treatment with a mAb F(ab')2 fragment recognizing CD45 phosphatase suppressed Fc gamma R-induced calcium mobilization in a dose-dependent manner. An ongoing intracellular calcium mobilization was immediately terminated when activation was followed by co-cross-linking Fc gamma R and CD45. This suggests that the initial steps of Fc gamma R signal transduction pathways are influenced by the state of tyrosine phosphorylation. Combined cross-linking of both receptors, however, was hardly susceptible to CD45. Also, inhibition of respiratory burst by CD45 in the case of Fc gamma RIIIb was minimal compared with that for Fc gamma RIIa. Signal transduction pathways of low affinity Fc gamma RIIa and Fc gamma RIIIb are differentially regulated by CD45, underlining the essential function of Fc gamma R-mediated tyrosine phosphorylation in polymorphonuclear neutrophil activation.
Hoffmeyer
F
F
Department of Medicine, Hannover Medical School, Germany.
Witte
K
K
Gebhardt
U
U
Schmidt
R E
RE
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D002118:Calcium / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D009504:Neutrophils / Q000378:metabolism* / Q000502:physiology; D017027:Protein Tyrosine Phosphatases / Q000276:immunology / Q000502:physiology*; D017452:Receptors, IgG / Q000378:metabolism*; D016897:Respiratory Burst / Q000187:drug effects*; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D017452:Receptors, IgG; D017027:Protein Tyrosine Phosphatases; D002118:Calcium