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Whereas the chemotactic peptide, N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMet-Leu-Phe), induced NADPH-oxidase-catalyzed superoxide (O2-) formation in human neutrophils, purine and pyrimidine nucleotides per se did not stimulate NADPH oxidase but enhanced O2- formation induced by submaximally and maximally stimulatory concentrations of fMet-Leu-Phe up to fivefold. On the other hand, FMet-Leu-Phe primed neutrophils to generate O2- upon exposure to nucleotides. At a concentration of 100 microM, purine nucleotides enhanced O2- formation in the effectiveness order adenosine 5'-O-[3-thio]triphosphate (ATP[gamma S]) greater than ITP greater than guanosine 5'-O-[3-thio]triphosphate (GTP[gamma S]) greater than ATP = adenosine 5'-O-[2-thio]triphosphate (Sp-diastereomer) = GTP = guanosine 5'-O-[2-thio]diphosphate (GDP[beta S] = ADP greater than adenosine 5'-[beta, gamma-imido]triphosphate = adenosine 5'-O-[2-thio]triphosphate] (Rp-diastereomer). Pyrimidine nucleotides stimulated fMet-Leu-Phe-induced O2- formation in the effectiveness order uridine 5'-O-[3-thio]triphosphate (UTP[gamma S]) = UTP greater than CTP. Uracil (UDP[beta S]) = uridine 5'-O[2-thio]triphosphate (Rp-diastereomer) (Rp)-UTP[beta S]) = UTP greater than CTP. Uracil nucleotides were similarly effective potentiators of O2- formation as the corresponding adenine nucleotides. GDP[beta S] and UDP[beta S] synergistically enhanced the stimulatory effects of ATP[gamma S], GTP[gamma S] and UTP[gamma S]. Purine and pyrimidine nucleotides did not induce degranulation in neutrophils but potentiated fMet-Leu-Phe-induced release of beta-glucuronidase with similar nucleotide specificities as for O2- formation. In contrast, nucleotides per se induced aggregation of neutrophils. Treatment with pertussis toxin prevented aggregation induced by both nucleotides and fMet-Leu-Phe. Our results suggest that purine and pyrimidine nucleotides act via nucleotide receptors, the nucleotide specificity of which is different from nucleotide receptors in other cell types. Neutrophil nucleotide receptors are coupled to guanine-nucleotide-binding proteins. As nucleotides are released from cells under physiological and pathological conditions, they may play roles as intercellular signal molecules in neutrophil activation.
R Seifert, and
K Wenzel, and
F Eckstein, and
G Schultz
May 1989,
The Biochemical journal,
R Seifert, and
K Wenzel, and
F Eckstein, and
G Schultz
November 1984,
Biochemical and biophysical research communications,
R Seifert, and
K Wenzel, and
F Eckstein, and
G Schultz
May 1990,
Biochimica et biophysica acta,
R Seifert, and
K Wenzel, and
F Eckstein, and
G Schultz
July 1994,
The Journal of biological chemistry,
R Seifert, and
K Wenzel, and
F Eckstein, and
G Schultz
September 1986,
FEBS letters,
R Seifert, and
K Wenzel, and
F Eckstein, and
G Schultz
October 2002,
European journal of immunology,
R Seifert, and
K Wenzel, and
F Eckstein, and
G Schultz
September 1984,
Federation proceedings,
R Seifert, and
K Wenzel, and
F Eckstein, and
G Schultz
October 1982,
The Journal of cell biology,
R Seifert, and
K Wenzel, and
F Eckstein, and
G Schultz
January 2003,
Experimental cell research,
R Seifert, and
K Wenzel, and
F Eckstein, and
G Schultz
January 2007,
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology,
