Dual effects of formylpeptides on the adhesion of endotoxin-primed human neutrophils.
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)
Bellavite
P
P
Istituto di Chimica e Microscopia Clinica, University of Verona, Italy.
Chirumbolo
S
S
Lippi
G
G
Andrioli
G
G
Bonazzi
L
L
Ferro
I
I
D015703:Antigens, CD / Q000032:analysis; D018845:CD11 Antigens; D018821:CD18 Antigens; D002448:Cell Adhesion / Q000187:drug effects*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D000242:Cyclic AMP / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004731:Endotoxins / Q000494:pharmacology*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015703:Antigens, CD; D018845:CD11 Antigens; D018821:CD18 Antigens; D004731:Endotoxins; D008070:Lipopolysaccharides; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D000242:Cyclic AMP; D013755:Tetradecanoylphorbol Acetate