Neutrophil stimulation: receptor, membrane, and metabolic events.
In the neutrophil, binding of ligands to their appropriate receptors initiates a sequence of events culminating in the physiological responses of aggregation, degranulation, and superoxide anion generation. Calcium has been proposed as a second messenger in the activation sequence of the neutrophil. Increments in cytosolic free calcium are one of the first measurable events subsequent to receptor occupancy, followed by enhanced plasmalemmal permeability to calcium, a process that may serve to enhance the physiological responses. In contrast to calcium, cyclic AMP (cAMP) does not act as a signal in the activation sequence of the neutrophil. Increments in cAMP that are triggered by complete secretagogues may act as an inhibitory feedback mechanism. Protein kinases, both cAMP- and calcium/phospholipid-sensitive enzymes, may play a role in the activation sequence. Phosphorylation of proteins occurs during neutrophil activation. A role for phosphatidylinositol/phosphatidic acid turnover in calcium gating has been proposed. In addition, modulation of phospholipids could serve to activate a protein kinase C. Finally, phospholipids can serve as a source for arachidonic acid, which is metabolized by a 5-lipoxygenase pathway in the neutrophil. Products of this pathway, such as leukotriene B4, may serve to mediate or modulate the activation sequence.
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002118:Calcium / Q000097:blood / Q000494:pharmacology; D002449:Cell Aggregation; D000242:Cyclic AMP / Q000097:blood; D006152:Cyclic GMP / Q000097:blood; D003594:Cytoplasmic Granules / Q000502:physiology; D006801:Humans; D008564:Membrane Potentials; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010743:Phospholipids / Q000097:blood; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D011955:Receptors, Drug / Q000502:physiology*; D013481:Superoxides / Q000097:blood
D001798:Blood Proteins; D010743:Phospholipids; D011955:Receptors, Drug; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D000242:Cyclic AMP; D011494:Protein Kinases; D006152:Cyclic GMP; D002118:Calcium