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

Extracellular nucleotide-induced 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 pharmacological profile of the P2Y2 receptor. Followed by generation of arachidonic acid, subsequently metabolized by 5 lipoxygenase forming the leukotrienes (LT). Of the several LTs generated, LTB(4)is a potent chemokine and upon its release binds to the PMN in an autocrine manner leading to the PMN degranulation. It is known that LTB(4)causes neutrophil degranulation through its receptor specific binding while the molecular mechanism remains not known at present. However, it is not known whether any LTB(4)receptor exists in cytoplasm in any given cell type and also, the existence of any other signaling cascade for the extracellular nucleotide-induced neutrophil degranulation. Based on the few direct experimental and numerous circumstantial evidence, it is conceivable that the extracellular nucleotides require LT generation, as an essential intermediate for mediating neutrophil degranulation. Copyright 2001 Harcourt Publishers Ltd.