Human GM-CSF primes neutrophils for enhanced oxidative metabolism in response to the major physiological chemoattractants.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a T cell-derived lymphokine which induces hematopoietic precursor cells to proliferate in vitro and differentiate to neutrophils and macrophages. GM-CSF also inhibits the motility of mature neutrophils (NIF-T activity), and primes neutrophils to enhance oxidative metabolism in response to the bacterial chemoattractant, N-formyl-methionyl-leucyl-phenylalanine (f-MLP). The present study was designed to determine whether this lymphokine also enhances neutrophil oxidative metabolism in response to the other major physiological chemoattractants which include complement-derived C5a, and the 5-lipoxygenation product of arachidonic acid, leukotriene B4 (LTB4). Superoxide anion production was measured as superoxide dismutase-inhibitable cytochrome C reduction. Purified biosynthetic GM-CSF enhanced superoxide anion production by neutrophils in response to f-MLP, C5a desArg, and LTB4. In contrast to several other factors which prime neutrophils, GM-CSF did not prime for an enhanced oxidative response to phorbol myristate acetate (PMA). These results suggest that GM-CSF may be an endogenous regulator of neutrophil inflammatory responses induced by the major physiological chemoattractants.
D002630:Chemotactic Factors / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003182:Complement C5 / Q000494:pharmacology; D015936:Complement C5a; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D007975:Leukotriene B4 / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002630:Chemotactic Factors; D003182:Complement C5; D007377:Interleukin-3; D013481:Superoxides; D007975:Leukotriene B4; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a; D013755:Tetradecanoylphorbol Acetate