Signal transduction events in stimulated rat neutrophils: effects of adenine nucleotides.
When rat neutrophils were stimulated with chemotactic peptide N-formyl-Met-Leu-Phe; fMLP), phorbol myristate acetate (PMA), or immune complexes in the presence of homologous platelets, O2- responses were enhanced. Secretion products of thrombin-stimulated platelets as well as ATP, ATP gamma S, or ADP enhanced O2- responses of fMLP-stimulated neutrophils, although these nucleotides did not, by themselves, initiate an O2- response. Calcium transients were measured in neutrophils which were stimulated with fMLP under a variety of conditions (+/- ATP gamma S, +/- cytochalasin B) which enhance O2- responses. Neutrophils incubated with ATP gamma S alone developed brief calcium transients similar to those produced by fMLP. As compared to changes in intracellular calcium in fMLP-stimulated neutrophils, the copresence of ATP gamma S with fMLP did not cause a statistically significant difference in the calcium transients, even though O2- production was enhanced. In contrast, in the presence of cytochalasin B, the addition of ATP gamma S to fMLP-stimulated neutrophils produced greatly sustained and protracted elevations in intracellular calcium, correlating with further enhancement of O2- responses. In fMLP-stimulated neutrophils the latter phases of the calcium transients appeared to be dependent in part on the availability of extracellular calcium. These data suggest that ATP gamma S-induced enhancement of O2- responses in fMLP-stimulated rat neutrophils may be related to two mechanisms, one being independent of fMLP-induced intracellular calcium transients and the other, which is related to the presence of cytochalasin B, being linked to sustained elevations in intracellular calcium associated with mobilization of extracellular calcium.
Ward
P A
PA
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109.
Cunningham
T W
TW
Johnson
K J
KJ
D000227:Adenine Nucleotides / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000502:physiology; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D002474:Cell-Free System; D003593:Cytoplasm / Q000502:physiology; D005110:Extracellular Space / Q000502:physiology; D008297:Male; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*; D010529:Peritoneal Cavity; D051381:Rats; D015398:Signal Transduction; D013481:Superoxides / Q000096:biosynthesis
D000227:Adenine Nucleotides; D013481:Superoxides; C022571:adenosine 5'-O-(3-thiotriphosphate); D000255:Adenosine Triphosphate; D002118:Calcium