Alteration of the functional effects of granulocyte-macrophage colony-stimulating factor on polymorphonuclear leukocytes by membrane-fluidizing agents.
Locomotion and oxidative metabolism of polymorphonuclear leukocytes from 15 patients receiving recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) were examined in vitro. At the end of each GM-CSF treatment course, polymorphonuclear leukocyte (PMN) chemotactic responses were suppressed and no enhancement of formyl-peptide-stimulated superoxide production was observed. The priming of PMN superoxide production normally seen after in vitro GM-CSF exposure was also blunted in these cells. By using control donor PMN, two membrane-fluidizing agents, pentoxifylline and butanol, were shown to normalize suppressed PMN chemotaxis caused by in vitro GM-CSF (1 nM) exposure. Pentoxifylline, but not butanol, also reversed the effects of in vitro GM-CSF on PMN superoxide production. When PMN obtained from six patients at the end of GM-CSF therapy were exposed to pentoxifylline in vitro, the chemotactic suppression typically observed was significantly improved. The data suggest that GM-CSF may affect PMN function via mechanisms involving membrane fluidity or cell deformability or both.
Buescher
E S
ES
Department of Pediatrics, University of Texas Medical School, Houston.
McIlheran
S M
SM
Banks
S M
SM
Vadhan-Raj
S
S
D020001:1-Butanol; D000440:Butanols / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000627:therapeutic use*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000627:therapeutic use*; D006801:Humans; D066298:In Vitro Techniques; D008560:Membrane Fluidity / Q000187:drug effects*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000276:immunology*; D010431:Pentoxifylline / Q000494:pharmacology*; D012509:Sarcoma / Q000188:drug therapy; D013481:Superoxides / Q000378:metabolism; D013805:Theobromine / Q000031:analogs & derivatives*
D000440:Butanols; D003115:Colony-Stimulating Factors; D006133:Growth Substances; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D020001:1-Butanol; D013805:Theobromine; D010431:Pentoxifylline