Endothelin-1 enhances superoxide generation of human neutrophils stimulated by the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine.
Endothelin-1 (ET-1) by itself was not an effective stimulus for inducing the superoxide (O2-) generation of human neutrophils, but it enhanced the O2- generation stimulated by the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) about 2-fold when the cells had been preincubated with ET-1 for 10 min at 37 degrees C. The concentration at which ET-1 was 50% effective was 1 x 10(-10) M, and the maximal effect was obtained at 1 x 10(-8) M. The enhancement was observed over the range of the effective concentrations of FMLP (10(-8)-10(-6) M). ET-1 did not promote the mobilization of intracellular calcium ions and the enhancing effect of ET-1 did not change when calcium ions were depleted. These findings indicate that ET-1 is a potent modulator of human neutrophils and may thus contribute to the inflammatory process.
Ishida
K
K
Department of Biochemistry, Kyushu University School of Medicine, Fukuoka, Japan.
Takeshige
K
K
Minakami
S
S
D002118:Calcium / Q000378:metabolism; D016232:Endothelins / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D013481:Superoxides / Q000097:blood*
D016232:Endothelins; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D010100:Oxygen; D002118:Calcium