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  • Title: Granulocyte and granulocyte-macrophage colony-stimulating factors exert differential effects on neutrophil platelet-activating factor generation and release.
    Author: Stewart AG, Cotterill T, Harris T.
    Journal: Immunology; 1994 May; 82(1):51-6. PubMed ID: 7519173.
    Abstract:
    The haemopoietic recombinant human cytokines granulocyte and granulocyte-macrophage colony-stimulating factor (rhG-CSF and rhGM-CSF) are used to facilitate recovery of bone marrow function following cytotoxic chemotherapy. Recent clinical experience indicates that rhG-CSF is better tolerated than rhGM-CSF. Thus, we have compared the priming effects of rhG-CSF and rhGM-CSF on superoxide anion (O2-) generation and platelet-activating factor (PAF) synthesis by neutrophils. During a 60-min incubation of neutrophils with rhGM-CSF (1 nM) or recombinant human tumour necrosis factor-alpha (rhTNF-alpha; 0.3 nM), cell-associated PAF levels increased, and upon stimulation with FMLP (100 nM) there was a striking amplification of PAF formation (8-13-fold) and release (24-36-fold). In contrast, in rhG-CSF (1 nM)-primed cells, there was no increase in cell-associated PAF levels and neither PAF synthesis nor PAF release was amplified following stimulation with FMLP. On the other hand, each of rhG-CSF, rhGM-CSF or rhTNF-alpha increased subsequent FMLP (100 nM)-induced O2- generation (by 89%, 166% and 115%, respectively). These results suggest the existence of distinct intracellular signalling pathways for cytokine priming. Furthermore, some of the more severe adverse reactions to the administration of rhGM-CSF may be a result of the biosynthesis and/or release of the potent inflammatory mediator, PAF.
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