P. Bellavite et al., DUAL EFFECTS OF FORMYLPEPTIDES ON THE ADHESION OF ENDOTOXIN-PRIMED HUMAN NEUTROPHILS, Cell biochemistry and function, 11(4), 1993, pp. 231-239
Neutrophils, treated with sequential additions of bacterial products s
uch as endotoxin (E. Coli lipopolysaccharide, LPS) and the chemotactic
peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP), undergo to me
tabolic activation and express membrane-anchoring proteins that promot
e adhesion to serum-coated culture wells. By investigating the dose-re
sponse relationships of these phenomena, we have found that: (a) resti
ng neutrophils do not produce a significant amount of superoxide (O-2(
-)) and show only minimal adhesion to serum-coated plastic surfaces; (
b) fully activatory doses (> 5 x 10(-8)M) of fMLP induce the release o
f O-2(-) and a significant increase of the cell adhesion; (c) pretreat
ment of the cells for 1 h with LPS augments cell adhesion to serum-coa
ted culture wells in the absence of further stimulation and primes the
neutrophils to enhanced fMLP-dependent O-2(-) release; (d) addition o
f low, substimulatory doses of fMLP (from 10(-10)M to 5 x 10(-9)M) inh
ibits and reverses the adhesion of LPS-treated cells, (e) high fMLP do
ses (> 10(-7)M) are additive to LPS in promoting adhesion. Phorbol-myr
istate acetate(> 10(-9)M) increased adhesion in both normal and LPS-tr
eated neutrophils, but low doses of this stimulant did not inhibit adh
esion. Low doses (10(-9)M) of fMLP increased intracellular cyclic AMP
in both normal and LPS-treated neutrophils, suggesting that stimulus-i
nduced rises in cAMP may be the negative signal responsible for down-m
odulation of adhesion. Low (5 x 10(-9)M) and high (5 x 10(-7)M) fMLP d
oses induced the same increase of expression of CD11/CD18 integrins, i
ndicating that the inhibition of adhesion caused by low doses is not d
ue to quantitative down-regulation of integrins. These findings may pr
ovide an in vitro model of the complex biological events involved in t
he regulation of neutrophil adhesion.