Chemoattractant receptors on phagocytic cells.
Chemoattractant receptors on leukocytes can trigger a number of cellular responses, including the cytoskeletal reorganization, changes in cell shape, directed motility, lysosomal enzyme secretion, and activation of the respiratory burst. The dose of chemoattractants required to induce motility-related functions is generally at least ten-fold smaller than the dose required to initiate secretory and respiratory burst activities. This finding and other pharmacological evidence clearly indicate that the two types of functions (i.e. motility and secretion) are regulated differently and can be divergently modified by drugs. The affinity of the oligopeptide chemoattractant receptor on polymorphonuclear leukocytes and macrophages is heterogeneous and dynamically regulated by guanine nucleotides and prior agonist exposure. High- and low-affinity forms of the oligopeptide receptor have been identified by direct binding studies. Our data suggest that low doses of agonists can initiate interconversion of low- and high-affinity states of that portion of chemoattractant receptors regulated by guanine nucleotides. On the other hand, high doses of agonists sufficient to induce chemotactic desensitization, lysosomal enzyme secretion, and the respiratory burst lead to the formation of a new population of high-affinity receptors. These binding sites are insensitive to the effects of guanine nucleotides and appear to be rapidly internalized. Transmethylation reactions mediated by S-adenosyl methionine are required for the activation of a phospholipase and release of arachidonate from leukocytes by chemotactic factors. We suggest that release of arachidonate from membrane phospholipid activates and translocates a cytosolic but loosely membrane-associated protein kinase C into the membrane and that this kinase participates in stimulus-response coupling of chemoattractant receptors.
D000818:Animals; D002465:Cell Movement; D002630:Chemotactic Factors / Q000502:physiology*; D002634:Chemotaxis, Leukocyte; D003182:Complement C5 / Q000502:physiology; D015936:Complement C5a; D006150:Guanine Nucleotides / Q000502:physiology; D006801:Humans; D007975:Leukotriene B4 / Q000502:physiology; D046911:Macromolecular Substances; D008264:Macrophages / Q000502:physiology*; D008563:Membrane Lipids / Q000502:physiology; D008745:Methylation; D009504:Neutrophils / Q000502:physiology*; D011485:Protein Binding; D011493:Protein Kinase C / Q000502:physiology; D011971:Receptors, Immunologic / Q000502:physiology*
D002630:Chemotactic Factors; D003182:Complement C5; D006150:Guanine Nucleotides; D046911:Macromolecular Substances; D008563:Membrane Lipids; D011971:Receptors, Immunologic; D007975:Leukotriene B4; D015936:Complement C5a; D011493:Protein Kinase C