Neutrophil degranulation: coactivation of chemokine receptor(s) is required for extracellular nucleotide-induced neutrophil degranulation

Extracellular nucleotide-incluced stimulation of leukocytes and subsequent adhesion to endothelium plays a critical role in inflammatory diseases. The extracellular nucleotides stimulate a P2Y receptor on human PMN with the p harmacological profile of the P2Y2 receptor. Followed by generation of arac hidonic acid, subsequently metabolized by 5 lipoxygenase forming the leukot rienes (LT). Of the several LTs generated, LTB4 is a potent chemokine and u pon its release binds to the PMN in an autocrine manner leading to the PMN degranulation. It is known that LTB4 causes neutrophil degranulation throug h its receptor specific binding while the molecular mechanism remains not k nown at present. However, it is not known whether any LTB4 receptor exists in cytoplasm in any given cell type and also, the existence of any other si gnaling cascade for the extracellular nucleotide-induced neutrophil degranu lation. Based on the few direct experimental and numerous circumstantial ev idence, it is conceivable that the extracellular nucleotides require LT gen eration, as an essential intermediate for mediating neutrophil degranulatio n. (C) 2001 Harcourt Publishers Ltd.