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. 1999 Jan 15;337(Pt 2):185–192.

Monosodium urate-crystal-stimulated phospholipase D in human neutrophils.

J Marcil 1, D Harbour 1, M G Houle 1, P H Naccache 1, S Bourgoin 1
PMCID: PMC1219951  PMID: 9882614

Abstract

Protein kinase Calpha (PKCalpha) and small GTPases of the Rho and ADP-ribosylation factor (Arf) family are implicated in the regulation of phospholipase D1 (PLD1) activity. Although they are involved in fMet-Leu-Phe (fMLP)-mediated PLD activation, their role in monosodium urate (MSU)-stimulated PLD1 activity in human neutrophils is not clear. The translocation of PKCalpha, RhoA and Arf from the cytosol to the membranes was monitored. fMLP induced a cytochalasin B (CB)-dependent recruitment of Arf, RhoA and PKCalpha to neutrophil membranes. CB also increased the activation of PLD 10-fold. In contrast with fMLP, MSU stimulated a sustained and time-dependent relocalization of Arf and PKCalpha, but not of RhoA, to the membrane fraction. MSU-stimulated PLD was activated with a time course preceding membrane recruitment of Arf and PKCalpha in the absence of CB. Furthermore, MSU-induced PLD activation and the membrane recruitment of PKCalpha, but not that of Arf, were inhibited by CB. An anti-FcgammaRIIIB antibody, VIFcRIII, prevented the membrane relocalization of Arf and PKCalpha and the stimulation of the levels of tyrosine phosphorylation and of PLD activity induced by MSU. Erbstatin and ST-638, two inhibitors of tyrosine kinases, inhibited the MSU-induced translocation of Arf and PKCalpha but not MSU-induced tyrosine phosphorylation and PLD activation. Furthermore MSU crystals did not cause the tyrosine phosphorylation of PLD1. The present study indicates that soluble and particulate agonists show selectivity in inducing the translocation of RhoA in neutrophils and that the ability of MSU to increase PLD activation was independent of the membrane relocalization of Arf and PKCalpha.

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Selected References

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