Dual effects of formylpeptides on the adhesion of endotoxin-primed human neutrophils

Cell Biochem Funct. 1993 Dec;11(4):231-9. doi: 10.1002/cbf.290110403.

Abstract

Neutrophils, treated with sequential additions of bacterial products such as endotoxin (E. Coli lipopolysaccharide, LPS) and the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP), undergo to metabolic activation and express membrane-anchoring proteins that promote adhesion to serum-coated culture wells. By investigating the dose-response relationships of these phenomena, we have found that: (a) resting neutrophils do not produce a significant amount of superoxide (O2-) and show only minimal adhesion to serum-coated plastic surfaces; (b) fully activatory doses (> 5 x 10(-8) M) of fMLP induce the release of O2- and a significant increase of the cell adhesion; (c) pretreatment of the cells for 1 h with LPS augments cell adhesion to serum-coated culture wells in the absence of further stimulation and primes the neutrophils to enhanced fMLP-dependent O2- release; (d) addition of low, substimulatory doses of fMLP (from 10(-10) M to 5 x 10(-9) M) inhibits and reverses the adhesion of LPS-treated cells, (e) high fMLP doses ( > 10(-7) M) are additive to LPS in promoting adhesion. Phorbol-myristate acetate (> 10(-9) M) increased adhesion in both normal and LPS-treated neutrophils, but low doses of this stimulant did not inhibit adhesion. Low doses (10(-9) M) of fMLP increased intracellular cyclic AMP in both normal and LPS-treated neutrophils, suggesting that stimulus-induced rises in cAMP may be the negative signal responsible for down-modulation of adhesion.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / analysis
  • CD11 Antigens
  • CD18 Antigens
  • Cell Adhesion / drug effects*
  • Chemotaxis, Leukocyte / drug effects
  • Cyclic AMP / analysis
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Endotoxins / pharmacology*
  • Humans
  • Lipopolysaccharides / pharmacology*
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology*
  • Neutrophils / drug effects*
  • Superoxides / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • Antigens, CD
  • CD11 Antigens
  • CD18 Antigens
  • Endotoxins
  • Lipopolysaccharides
  • Superoxides
  • N-Formylmethionine Leucyl-Phenylalanine
  • Cyclic AMP
  • Tetradecanoylphorbol Acetate