Chemoattractant receptor affinity reflects its ability to transduce different biological responses.
The oligopeptide chemotactic factor receptor in human PMN membranes exists in two affinity states which are in part interconvertible and regulated by guanine nucleotides. In whole cells, only one affinity of the receptor can be seen, presumably due to the high intracellular levels of guanine nucleotides as well as rapidly ongoing cellular processes which allow the detection of only a single affinity state. There is strong evidence to suggest that the affinity of the chemoattractant receptor in whole PMNs can be modified by agents which alter the physical state of the PMN membrane. The average affinity of the oligopeptide chemotactic factor receptor can be enhanced by aliphatic alcohols which decrease membrane microviscosity. Under these conditions, chemotactic responsiveness of PMNs is enhanced but 0(2-) production and secretion initiated by chemoattractants is markedly depressed. When the affinity of the receptor is lowered as in the case of amphotericin B, chemotaxis is depressed but lysozyme secretion is enhanced. These data indicate that the transduction mechanisms for certain biological responses initiated by the chemoattractant receptor are heterogeneous. It can be hypothesized that the particular transduction pathway initiated by chemoattractant receptor occupancy is reflected by the affinity state of the receptor. The higher affinity state initiates chemotactic signals whereas the lower affinity state initiates 0(2-) production and secretion. By altering the affinity of the receptor using pharmacological means one may be able to modify the biological activity of human PMNs.
D000438:Alcohols / Q000494:pharmacology; D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D006150:Guanine Nucleotides / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology; D008560:Membrane Fluidity / Q000187:drug effects; D008715:Methionine / Q000031:analogs & derivatives*; D009239:N-Formylmethionine / Q000031:analogs & derivatives* / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009504:Neutrophils / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D044042:Receptors, Formyl Peptide
D000438:Alcohols; D006150:Guanine Nucleotides; D009842:Oligopeptides; D011956:Receptors, Cell Surface; D044042:Receptors, Formyl Peptide; D009239:N-Formylmethionine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D000666:Amphotericin B; D008715:Methionine