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Effects of recombinant human granulocyte‐macrophage colony‐stimulating factor (GM‐CSF rh ) on transmembrane electrical potentials in granulocytes: Relationship between enhancement of ligand‐mediated depolarization and augmentation of superoxide anion (O − 2 ) production
Author(s) -
Sullivan Richard,
Fredette Joseph P.,
Leavitt Julie L.,
Gadenne AnneSophie,
Griffin James D.,
Simons Elizabeth R.
Publication year - 1989
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041390219
Subject(s) - depolarization , superoxide , membrane potential , transmembrane protein , biophysics , respiratory burst , granulocyte , chemistry , recombinant dna , biochemistry , biology , microbiology and biotechnology , immunology , receptor , enzyme , gene
When human granulocytes that have been primed with recombinant human granulocyte–macrophage colony‐stimulating factor (GM‐CSF rh ) are activated by ligands that stimulate the respiratory burst, the amount of superoxide anion (O − 2 ) they generate is significantly increased. We have found that the accelerated rate of O − 2 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‐CSF rh ‐primed granulocytes and investigated its relationship to the increase in O − 2generation 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 valinornycin. When their ability to depolarize was virtually eliminated by dissipating the transmembrane K + gradient, GM‐CSF rh ‐pretreated cells continued to generate more O − 2after fMLP than did control cells. These results indicate that augmentation of the granulocyte's ability to generate O − 2anions, which is induced by priming with GM‐CSF rh , is independent both of the resting transmembrane potential and of alterations in the extent of membrane potential change induced by stimuli such as fMLP.