Effects of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSFrh) on transmembrane electrical potentials in granulocytes: relationship between enhancement of ligand-mediated depolarization and augmentation of superoxide anion (O2-) production.
When human granulocytes that have been primed with recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSFrh) are activated by ligands that stimulate the respiratory burst, the amount of superoxide anion (O2-) they generate is significantly increased. We have found that the accelerated rate of O2- release occurring under these conditions is accompanied by an antecedent increase in membrane depolarization. We examined the nature of the enhancement of membrane depolarization in GM-CSFrh-primed granulocytes and investigated its relationship to the increase in O2- generation by N-formyl methionylleucylphenylalanine (fMLP)-activated granulocytes. We found that augmented depolarization could not be accounted for by a change in the resting membrane potential induced by the growth factor and was still present after either blocking passive transmembrane Na+ movement with dimethylamiloride or by increasing the membrane's permeability to K+ with valinomycin. When their ability to depolarize was virtually eliminated by dissipating the transmembrane K+ gradient, GM-CSFrh-pretreated cells continued to generate more O2- after fMLP than did control cells. These results indicate that augmentation of the granulocyte's ability to generate O2- anions, which is induced by priming with GM-CSFrh, is independent both of the resting transmembrane potential and of alterations in the extent of membrane potential change induced by stimuli such as fMLP.
Sullivan
R
R
Department of Medicine, Boston University Medical School, Massachusetts.
Fredette
J P
JP
Leavitt
J L
JL
Gadenne
A S
AS
Griffin
J D
JD
Simons
E R
ER
D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006098:Granulocytes / Q000187:drug effects* / Q000378:metabolism; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D011994:Recombinant Proteins; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor