Inhibition of human neutrophil receptor-mediated uptake of N-formyl-met-leu-phe by platelet factor 4 (59-70)

Immunology. 1985 Jan;54(1):163-72.

Abstract

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).

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylglucosaminidase / metabolism
  • Chemotaxis, Leukocyte*
  • Glucuronidase / metabolism
  • Humans
  • Monocytes / immunology
  • N-Formylmethionine Leucyl-Phenylalanine / metabolism*
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Peptide Fragments / immunology*
  • Platelet Factor 4 / immunology*
  • Receptors, Immunologic / metabolism*

Substances

  • Peptide Fragments
  • Receptors, Immunologic
  • Platelet Factor 4
  • N-Formylmethionine Leucyl-Phenylalanine
  • platelet factor 4 (59-70)
  • Glucuronidase
  • Acetylglucosaminidase