1. Dual effects of formylpeptides on the adhesion of endotoxin-primed human neutrophils
- Author
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I. Ferro, Paolo Bellavite, G. Andrioli, L. Bonazzi, Giuseppe Lippi, and Salvatore Chirumbolo
- Subjects
Lipopolysaccharides ,Lipopolysaccharide ,Neutrophils ,Clinical Biochemistry ,Integrin ,CD18 ,Biochemistry ,chemistry.chemical_compound ,Hormesis ,Antigens, CD ,Superoxides ,Cell Adhesion ,Cyclic AMP ,Humans ,Adhesion ,Superoxide ,Neutrophil ,Cell adhesion ,Dose-Response Relationship, Drug ,biology ,CD11 Antigens ,Drug Synergism ,Chemotaxis ,Cell Biology ,General Medicine ,Molecular biology ,Endotoxins ,N-Formylmethionine Leucyl-Phenylalanine ,Chemotaxis, Leukocyte ,chemistry ,CD18 Antigens ,biology.protein ,Tetradecanoylphorbol Acetate ,lipids (amino acids, peptides, and proteins) ,Intracellular - 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 (O) and show only minimal adhesion to serum-coated plastic surfaces; (b) fully activatory doeses (> 5 × 10−8M) of fMLP induce the release of O 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 O release; (d) addition of low, substimulatory doses of fMLP (from 10−10M to 5 × 10−9M) inhibits and reverses the adhesion of LPS-treated cells, (e) high fMLP doses (> 10−7M) are additive to LPS in promoting adhesion. Phorbol-myristate acetate (> 10−9M) increased adhesion in both normal and LPS-treated neutrophils, but low doses of this stimulant did not inhibit adhesion. Low doses (10−9M) 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. Low (5 × 10−9M) and high (5 × 10−7M) fMLP doses induced the same increase of expression of CD11/CD18 integrins, indicating that the inhibition of adhesion caused by low doses is not due to quantitative down-regulation of integrins. These findings may provide an in vitro model of the complex biological events involved in the regulation of neutrophil adhesion.
- Published
- 1993