Inhibition of human neutrophil receptor-mediated uptake of N-formyl-met-leu-phe by platelet factor 4 (59-70).
Human platelet factor 4 (PF4) and a substituent dodecapeptide designated PF4(59-70) elicited human neutrophil and monocyte chemotaxis with a similar concentration-dependence and maximal responses equal to that attained by chemotactic fragments of C5 (C5fr). At maximally chemotactic concentrations, PF4(59-70) stimulated the secretion by neutrophils of approximately 40% and 60% of the respective quantities of beta-glucuronidase and beta-glucosaminidase released by 10(-6) M N-formyl-methionyl-leucyl-phenylalanine (fMLP). In contrast to the deactivation of chemotaxis achieved by preincubation of neutrophils with other chemotactic factors, prior exposure to 10(-6)M PF4(59-70) for 2 min, or 20 min at 37 degrees, enhanced by 1.5- to 2-fold the chemotactic responses of neutrophils evoked by optimal concentrations of fMLP, C5fr, leukotriene B4, and PF4(59-70). Concentrations of PF4(59-70) which enhanced neutrophil chemotaxis inhibited the rate of receptor-mediated internalization of [3H]fMLP at 37 degrees and 18 degrees, but at 0 degrees failed to alter the binding affinity or the number of receptors for [3H]fMLP. Preincubation of neutrophils at 37 degrees with concentrations of PF4(59-70) which enhanced neutrophil chemotaxis also did not affect the subsequent binding of [3H]fMLP at 0 degrees. The inhibition by PF4(59-70) of the receptor-mediated internalization of [3H]fMLP was not mimicked by other positively charged compounds. The specific inhibition of receptor-mediated internalization of fMLP may explain the enhanced chemotactic responsiveness of neutrophils preincubated with PF4(59-70).
D000118:Acetylglucosaminidase / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D009000:Monocytes / Q000276:immunology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology*; D010978:Platelet Factor 4 / Q000276:immunology*; D011971:Receptors, Immunologic / Q000378:metabolism*
D010446:Peptide Fragments; D011971:Receptors, Immunologic; D010978:Platelet Factor 4; D009240:N-Formylmethionine Leucyl-Phenylalanine; C044557:platelet factor 4 (59-70); D005966:Glucuronidase; D000118:Acetylglucosaminidase