Adaptation of human neutrophil responsiveness to the chemoattractant N-formylmethionylleucylphenylalanine. Heterogeneity and/or negative cooperative interaction of receptors.
The dose-response characteristics of the neutrophil 3-3'-dipentyloxacarbocyanine (di-O-C5(3)) fluorescence response to repetitive stimulation with the chemoattractant N-formylmethionylleucylphenylalanine (fMet-Leu-Phe) were studied. Neutrophils exposed to the chemoattractant fMet-Leu-Phe at less than 5 X 10(-8) M subsequently responded only to higher concentrations of fMet-Leu-Phe. This stimulus-induced modification of neutrophil responsiveness involved a reversible fMet-Leu-Phe-induced shift in response Km (the concentration of fMet-Leu-Phe producing a half-maximal response) to higher values which occurred 1 to 2 min after exposure to fMet-Leu-Phe and represented a form of adaptation. A Hill coefficient of 0.68 +/- 0.07 was determined from analysis of the data indicating that the di-O-C5(3) fluorescence response behavior is compatible with functional negatively cooperative interaction and/or heterogeneity of fMet-Leu-Phe receptors. In related studies, analysis of the binding of fMet-Leu-[3H]Phe to intact cells and cell-free plasma membrane preparations resulted in Hill coefficients of 0.64 +/- 0.06 and 0.69 +/- 0.07, respectively, indicating that fMet-Leu-Phe binding exhibits properties similar to the fMet-Leu-Phe-elicited di-O-C5(3) fluorescence response. Modulation of receptor affinity, through either negative cooperativity or changing populations of heterogeneous receptors, may be an important mechanism by which neutrophils adapt and respond to a gradient of chemoattractant during the process of chemotaxis.
D002630:Chemotactic Factors / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008715:Methionine / Q000031:analogs & derivatives*; D009239:N-Formylmethionine / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D009842:Oligopeptides / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D044042:Receptors, Formyl Peptide; D013050:Spectrometry, Fluorescence
D002630:Chemotactic Factors; D009842:Oligopeptides; D011956:Receptors, Cell Surface; D044042:Receptors, Formyl Peptide; D009239:N-Formylmethionine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D008715:Methionine