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

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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 × 10−8 M) 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 10−10 M to 5 × 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 (> 10−9M) 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. Low (5 × 10−9 M) and high (5 × 10−7 M) 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.