CYCLIC AMP-INDEPENDENT ACTIVATION OF NEUTROPHIL-LIKE HL-60 CELLS BY PROSTAGLANDIN E-2

The role of cAMP in mediating prostaglandin E-2(PGE(2))-stimulated agg regation of neutrophil like HL-60 cells has been investigated. Althoug h the EP2 receptors appear to couple to G(s),-proteins, PGE(2) stimula ted HL-60 cell aggregation appears to be a cAMP-independent process. T his response to PGE(2) is independent oi calcium and tyrosine kinase a ctivity, appears to involve activation of phosphatidylinositol ? kinas e which is negatively regulated by phosphatidic acid generated from ph ospholipase D activity, and is partially dependent on protein kinase C activity. In contrast, although the chemotactic peptide N-formyl-meth ionyl-leucyl-phenyl-alanine (FMLP) produces a similar aggregation resp onse to PGE(2), FMLP uses a distinct intracellular signalling pathway. The aggregation response to FMLP involves activation of G(1)-proteins , is partially dependent on extracellular calcium, is negatively regul ated by protein kinase C, and is independent of phosphatidylinositol 3 -kinase, phospholipase D and tyrosine kinase activity. The possibility exists that EP2 receptor activation leads to G(s)-dependent, but cAMP independent, stimulation of phosphatidylinositol 3-kinase activity in HL-60 cells. (C) 1997 Elsevier Science Inc.