These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Abnormal response to granulocyte colony-stimulating factor (G-CSF) in canine cyclic hematopoiesis is not caused by altered G-CSF receptor expression.
    Author: Avalos BR, Broudy VC, Ceselski SK, Druker BJ, Griffin JD, Hammond WP.
    Journal: Blood; 1994 Aug 01; 84(3):789-94. PubMed ID: 7519075.
    Abstract:
    A decrease in responsiveness to granulocyte colony-stimulating factor (G-CSF) has been implicated in the pathophysiology of cyclic hematopoiesis. Using the canine model of cyclic neutropenia, we examined the response of neutrophil precursors to G-CSF in vitro and G-CSF receptor expression in neutrophils from grey collie dogs to determine whether the abnormal response observed to G-CSF in vivo in this disorder is present at the level of the progenitor cell and is caused by defective G-CSF receptor expression. Bone marrow mononuclear cells from grey collie dogs required sevenfold higher G-CSF concentrations than normal dog cells to achieve half-maximal colony growth [56 pmol/L v 8 pmol/L). Receptor binding assays with 125I-labeled G-CSF and Scatchard analyses of the equilibrium binding data were consistent with expression of a single class of high-affinity receptors for G-CSF on neutrophils from both normal dogs and grey collies with similar receptor numbers (56 to 446 sites/cell v 78 to 199 sites/cell) and binding affinities (28 to 206 pmol/L v 84 to 195 pmol/L). Chemical cross-linking studies identified a G-CSF binding protein of approximately 120 kD on neutrophils from grey collies, similar in size to that on normal dog neutrophils. No abnormal G-CSF receptor mRNA transcripts were detected in neutrophils from grey collie dogs by Northern blot analysis. Treatment of both normal and grey collie neutrophils with G-CSF rapidly induced tyrosine phosphorylation of an 80-kD protein that behaved like canine c-rel. These results demonstrate that the abnormal responsiveness to G-CSF in canine cyclic hematopoiesis is present in neutrophil precursors and is not associated with demonstrable alterations in the number, binding affinity, or overall size of the G-CSF receptor in neutrophils, or with defective tyrosine phosphorylation of p80. These data suggest that cyclic hematopoiesis is caused by a defect in the G-CSF signal transduction pathway at a point distal to G-CSF receptor binding that does not involve the early biochemical events leading to p80 tyrosine phosphorylation.
    [Abstract] [Full Text] [Related] [New Search]