Neutrophil chemotaxis: potential role of chemokine receptors in extracellular nucleotide induced Mac-1 expression.
Extracellular nucleotide-induced stimulation and activation of neutrophil in the inflammatory foci followed by chemotaxis in to inflamed vasculature plays a critical role in inflammatory diseases and coronary artery diseases. The extracellular nucleotides stimulate a P2Y receptor(s) on human PMN with the pharmacological profile similar to that of the P2Y2 receptor. Consequent to the activation of P2Y2, arachidonic acid is formed from the membrane bound lipids by phospholipase A2, which subsequently metabolized by 5 lipoxygenase to form the leukotrienes. Of the several leukotrienes generated, LTB(4) is a potent proinflammatory chemokine. Upon its release LTB(4) binds to the PMN by autocrine manner in the same neutrophil and also in a paracrine manner to other neutrophils, leading to the accelerated Mac-1 expression on PMN membrane resulting chemotaxis. Thus it is suggested that the extracellular nucleotide(s) released from the activated platelets and other damaged cell types exacerbate inflammatory response by leukotriene generation. In turn the leukotriene will act in both autocrine and paracrine manner to amplify the process of chemotaxis in PMN by upregulation of Mac-1 expression.
Temple University, Philadelphia, PA, USA. sukannan@utmb.edu
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D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism; D019556:COS Cells; D045744:Cell Line, Tumor; D002633:Chemotaxis; D004789:Enzyme Activation; D006801:Humans; D007249:Inflammation; D015289:Leukotrienes / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000096:biosynthesis*; D008962:Models, Theoretical; D009504:Neutrophils / Q000166:cytology*; D019707:Receptors, Chemokine / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058473:Receptors, Purinergic P2Y2; D015398:Signal Transduction; D015854:Up-Regulation
D015289:Leukotrienes; D016177:Macrophage-1 Antigen; C546385:P2RY2 protein, human; D019707:Receptors, Chemokine; D018048:Receptors, Purinergic P2; D058473:Receptors, Purinergic P2Y2; D016718:Arachidonic Acid; D001094:Arachidonate 5-Lipoxygenase