Granulocyte/macrophage colony-stimulating factor primes human neutrophils for increased diacylglycerol generation in response to chemoattractant.
Pretreatment of human neutrophils with granulocyte macrophage-colony stimulating factor (GM-CSF) augments several biological responses to chemoattractants (e.g. the respiratory burst, degranulation, and chemotaxis). However, little is known regarding the intracellular effects of priming with GM-CSF. In the present study, we have investigated the effects of GM-CSF on the generation of diacylglycerol (DAG), a proposed mediator of neutrophil responses. GM-CSF alone produced only a small increase in cellular DAG mass, which was most apparent after 30 min. GM-CSF pretreatment (60 min), however, caused a striking augmentation in DAG generation in response to the chemoattractant formyl-methionyl-leucyl-phenylalanine (fMLP), compared with neutrophils preincubated without GM-CSF. The augmentation in DAG generation correlated with an enhancement by GM-CSF of superoxide generation in response to fMLP. The data suggest that GM-CSF may exert some of its biological effects by enhancing DAG generation in response to a second agonist.
Tyagi
S R
SR
Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322.
Winton
E F
EF
Lambeth
J D
JD
D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D004075:Diglycerides / Q000097:blood*; D005989:Glycerides / Q000097:blood*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D013481:Superoxides / Q000097:blood
D003115:Colony-Stimulating Factors; D004075:Diglycerides; D005989:Glycerides; D006133:Growth Substances; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor