Abstract
Granulocyte-macrophage colony stimulating factor (GMCSF) promotes the growth of granulocytes and macrophages from undifferentiated bone marrow cells and modulates the oxidative responses of polymorphonuclear leukocytes (PMN) to endogenous chemoattractants. We found that,in vitro, naturally occurring glycolsylated human GMCSF does not disturb the resting canine PMN membrane potential, may attentuate PMN oxidative responses to PMA, and is, to a small degree, chemotaxigenic. GMCSF, however, inhibits PMN chemotaxis to zymosanactivated plasma (ZAP). Compared to temperature controls, GMCSF (1-100 U/ml) produced up to 1.5-fold increases in H2O2 production after 15 minutes, while phorbol myristate acetate (PMA) treated cells increased H2O2 production 8–12-fold after 15 minutes. Preincubation of cells with GMCSF (1–100 U/ml) prior to PMA stimulation significantly reduced the H2O2 levels induced by PMA. H202 production was inhibited up to 15% after 15 minutes of GMCSF preincubation and up to 40% after 60 minutes of preincubation. As a chemotaxigenic agent, GMCSF (10–1000 U/ml) was able to elicit 49%–102% increases in quantitative cellular migration, compared to random migration. Total cellular chemotaxis to GMCSF was < 30% of the response to ZAP. Preincubation of PMNs with GMCSF for 15 minutes significantly inhibited ZAP-induced cellular migration. Human GMCSF does not appear to activate canine PMNin vitro and may actually down-regulate PMN inflammatory responses.
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Abbreviations
- FL:
-
fluorescence intensity
- GMCSF:
-
granulocyte-macrophage colony-stimulating Factor
- HBSS:
-
Hanks balanced salt solution
- H2O2 :
-
hydrogen peroxide
- MP:
-
membrane potential
- PMA:
-
phorbol myristate acetate
- PMN:
-
polymorphonuclear leukocyte
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Supported by the Armed Forces Radiobiology Research Institute, Defense Nuclear Agency, under work unit No. 00082. Views presented in this paper are those of the authors; no endorsement by the Defense Nuclear Agency has been given or should be inferred. Research was conducted according to the principles enunciated in the “Guide for the Care and Use of Laboratory Animals” prepared by the Institute of Laboratory Animal Resources, National Research Council.
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D'Alesandro, M.M., Gruber, D.F., O'Halloran, K.P. et al. In vitro modulation of canine polymorphonuclear leukocyte function by granulocyte-macrophage colony stimulating factor. Biotherapy 3, 233–239 (1991). https://doi.org/10.1007/BF02171686
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DOI: https://doi.org/10.1007/BF02171686