title: Specific receptor sites for chemotactic peptides on human polymorphonuclear leukocytes.
abstract: Synthetic N-formylmethionyl peptides are chemotactic attractants for human polymorphonuclear leukocytes. The well-defined structure-activity relationship of these peptides in eliciting a chemotactic response suggests that the interaction of the peptides with a specific cellular binding site may initiate chemotaxis. By using tritiated N-formylmethionyl-leucyl-phenylalanine (fMet-Leu-[3H]Phe), a potent chemotactic peptide with high specific radioactivity, we have directly identified binding sites on human polymorphonuclear leukocytes. Binding of fMet-Leu-[3H]Phe to polymorphonuclear leukocytes is rapid (t1/2  less than 2 min) and reversible. The equilibrium dissociation constant (KD) for the interaction of fMet-Leu-[3H-A1Phe with the binding site is 12-14 nM at 37 degrees. The number of binding sites is approximately 2000 per cell. The specificity of the binding sites for a series of N-formylmethionyl peptides exactly reflects the specificity of the chemotactic response to the peptides in that they compete for the binding sites and initiate chemotaxis with the same order of potency (fMet-Leu-Phe greater than fMet-Met-Met greater than fMet-Phe greater than fMet-Leu greater than fMet),fPhe-Met is a competitive antagonist of the chemotactic activity of N-formylmethionyl peptides and has a calculated KD of 6x10-5 M. FPhe-Met also half-maximally inhibits binding of fMet-Leu[3H]Phe binding was the highest in polymorphonuclear leukocytes. No binding of fMet-Leu-[3H]Phe to human erythrocytes could be detected. These data indicate that fMet-Leu-[3H]Phe can be used to identify binding sites for chemotactic peptides on human polymorphonuclear leukocytes. It is likely that these binding sites initiate the specific response of motile cells to N-formylmethionyl peptides.
mesh_terms: D001665:Binding Sites; D002634:Chemotaxis, Leukocyte; D006801:Humans; D007700:Kinetics; D008214:Lymphocytes / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D009842:Oligopeptides
references.citation: Proc Natl Acad Sci U S A. 1975 Mar;72(3):1059-62
references.pmid: 1093163
references.citation: Scand J Clin Lab Invest Suppl. 1968;97:77-89
references.pmid: 4179068
references.citation: Science. 1968 Oct 18;162(3851):361-3
references.pmid: 4175690
references.citation: J Clin Invest. 1976 Jan;57(1):149-55
references.pmid: 1245597
references.citation: Science. 1976 May 21;192(4241):791-3
references.pmid: 4894
references.citation: Infect Immun. 1975 Mar;11(3):488-92
references.pmid: 46841
references.citation: J Exp Med. 1968 Aug 1;128(2):259-75
references.pmid: 4873021
references.citation: Proc Natl Acad Sci U S A. 1976 Jul;73(7):2439-42
references.pmid: 1065899
references.citation: J Exp Med. 1976 May 1;143(5):1154-69
references.pmid: 1262785
references.citation: Nature. 1975 Jul 17;256(5514):213-5
references.pmid: 1152991
references.citation: J Exp Med. 1975 Jun 1;141(6):1437-41
references.pmid: 1127383
references.citation: Ann N Y Acad Sci. 1967 Feb 10;139(3):553-70
references.pmid: 5232334