1720802

pubmed:Citation

6

Recombinant human granulocyte-colony stimulating factor (G-CSF) and recombinant human granulocyte/macrophage-colony stimulating factor (GM-CSF) stimulate neutrophil production from precursors in the marrow and enhance granulocyte functions in vitro. We studied the effects of G-CSF and GM-CSF on neutrophil superoxide production and secretion. G-CSF and GM-CSF alone stimulated neither superoxide production nor secretion, but both agents primed neutrophils for superoxide production stimulated by either N-formylmethionyl-leucyl-phenylalanine (FMLP) or ionomycin. Optimal priming occurred with G-CSF at 5.3 ng/ml for 20 minutes and for GM-CSF at 1 ng/ml for 60 minutes. Priming by GM-CSF was more readily inhibited by the tyrosine kinase inhibitor ST638 but was unaffected by staurosporine. Conversely, G-CSF priming was inhibited by staurosporine but not by ST638. Neither protein kinase C translocation nor increased protein kinase C activity, however, were observed after G-CSF/GM-CSF treatment. Priming by G-CSF and GM-CSF was sensitive to pertussis toxin, suggesting the involvement of guanine nucleotide-binding proteins (G-proteins). Neutrophils from three siblings with cyclic neutropenia were studied to observe the effects of G-CSF treatment on neutrophil function in vivo; sibling 1 and sibling 2 were treated with G-CSF for 6 months, but sibling 3 was not in the treatment group. Compared with neutrophils from normal donors, neutrophils from sibling 1 and sibling 2 were primed in vivo for superoxide release stimulated by either ionomycin or FMLP. Superoxide released by neutrophils from sibling 3 was similar to control cells.(ABSTRACT TRUNCATED AT 250 WORDS)

eng

AIM

MEDLINE

0022-2143

Print

NLM

576-84

pubmed-meshheading:1720802-Alkaloids, pubmed-meshheading:1720802-Cinnamates, pubmed-meshheading:1720802-Dose-Response Relationship, Drug, pubmed-meshheading:1720802-GTP-Binding Proteins, pubmed-meshheading:1720802-Granulocyte Colony-Stimulating Factor, pubmed-meshheading:1720802-Granulocyte-Macrophage Colony-Stimulating Factor, pubmed-meshheading:1720802-Humans, pubmed-meshheading:1720802-Ionomycin, pubmed-meshheading:1720802-N-Formylmethionine Leucyl-Phenylalanine, pubmed-meshheading:1720802-Neutrophils, pubmed-meshheading:1720802-Protein Kinase Inhibitors, pubmed-meshheading:1720802-Protein-Tyrosine Kinases, pubmed-meshheading:1720802-Recombinant Proteins, pubmed-meshheading:1720802-Respiratory Burst, pubmed-meshheading:1720802-Signal Transduction, pubmed-meshheading:1720802-Staurosporine, pubmed-meshheading:1720802-Sulfides, pubmed-meshheading:1720802-Superoxides

Recombinant human G-CSF and GM-CSF prime human neutrophils for superoxide production through different signal transduction mechanisms.

Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S.