Temperature-dependent inhibition of fmet-leu-phe-stimulated superoxide generation by C-I and H-7 in human neutrophils.
Contrary to previous reports by other investigators, protein kinase inhibitors C-I and H-7 (at 10(-6)M) caused a significant inhibition of fmet-leu-phe-stimulated superoxide (O2-) generation in human neutrophils. The observed inhibition of O2- production was a highly temperature-sensitive event and occurred only when C-I or H-7 was added to neutrophils at 37 degrees C. When the temperature at which C-I or H-7 added to neutrophils was varied between 16 degrees C to 37 degrees C, no significant inhibition of fmet-leu-phe-stimulated O2- production by C-I or H-7 was observed even at 35 degrees C. However, when added at 37 degrees C, both the maximal rate and the final extent of fmet-leu-phe induced O2- production were significantly inhibited (greater than 50%) by 10(-6)M C-I or H-7. A relatively weaker protein kinase C antagonist, HA1004, was not inhibitory under identical experimental conditions. In contrast, inhibition of the PMA-induced O2- generation by C-I or H-7 was not found to be similarly temperature-dependent. These results indicate that some temperature-dependent cellular event(s) is critically involved in the observed inhibition of fmet-leu-phe-induced O2- generation by C-I or H-7, and suggest a role for protein kinase C in the signal transduction process.
Nath
J
J
Department of Hematology, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
Powledge
A
A
D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000378:metabolism*; D047428:Protein Kinase Inhibitors; D013481:Superoxides / Q000378:metabolism*; D013696:Temperature
D047428:Protein Kinase Inhibitors; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine