Calcium mobilization and signal transduction in the neutrophils.
Neutrophil responsiveness is initiated by increases in the intracellular concentration of calcium through mechanisms the elucidation of which is of interest to the field of signal transduction in calcium mobilizing systems. Some, but not all, neutrophil chemotactic factors specifically stimulate the hydrolysis of phosphatidylinositol 4,5-bisphosphate. A non-mitochondrial pool of internal calcium has been shown to be released in permeabilized cells by inositol 1,4,5-trisphosphate. Diglyceride is thought to activate protein kinase C producing stimulatory and inhibitory signals for neutrophil activation. The lack of effect of leukotriene B4, on polyphosphoinositide hydrolysis indicates that mechanisms independent of inositol 1,4,5-trisphosphate are also available to the neutrophils. Pertussis toxin inhibits the stimulated mobilization of calcium, hydrolysis of the polyphosphoinositides and activation of protein kinase C. The inhibitory effects of pertussis toxin can be bypassed by phorbol esters and calcium ionophores thus indicating that a guanine nucleotide binding protein is functionally located at a step preceding the activation of phospholipase C. The similarities between the biochemical events activated by chemotactic factors and those described in other hormonally sensitive cells emphasize the generality of the relevance of these concepts. The differences raise the possibility that elements of the excitation-response coupling sequence other than those commonly monitored will still be identified. The later may be more evident in the neutrophils because these cells' predominant function is motility and not secretion.
D002118:Calcium / Q000097:blood*; D019204:GTP-Binding Proteins / Q000097:blood; D006706:Homeostasis; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000097:blood; D011493:Protein Kinase C / Q000097:blood
D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D002118:Calcium