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 an d cross-linking of the low affinity Fc gamma RIIa and Fc gamma RIIIb u sing mAb Fab and F(ab')(2) fragments led to transient intracellular ca lcium mobilization and activation of the respiratory burst. Fc gamma R IIIb engagement resulted in a different pattern of intracellular calci um flux, and induction of the respiratory burst was significantly more effective than in the case of Fc gamma RIIa. These data demonstrate t hat 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-induc ed calcium mobilization in a dose-dependent manner. An ongoing intrace llular calcium mobilization was immediately terminated when activation was followed by co-cross-linking Fc gamma R and CD45. This suggests t hat the initial steps of Fc gamma R signal transduction pathways are i nfluenced by the state of tyrosine phosphorylation. Combined cross-lin king 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 differe ntially regulated by CD45, underlining the essential function of Fc ga mma R-mediated tyrosine phosphorylation in polymerphonuclear neutrophi l activation.