scholarly journals Abnormal response to granulocyte colony-stimulating factor (G-CSF) in canine cyclic hematopoiesis is not caused by altered G-CSF receptor expression

Blood ◽  
1994 ◽  
Vol 84 (3) ◽  
pp. 789-794 ◽  
Author(s):  
BR Avalos ◽  
VC Broudy ◽  
SK Ceselski ◽  
BJ Druker ◽  
JD Griffin ◽  
...  
Keyword(s):  
Tyrosine Phosphorylation ◽  
Receptor Binding ◽  
Receptor Expression ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Cyclic Neutropenia ◽  
Abnormal Response ◽  
Cyclic Hematopoiesis ◽  
Stimulating Factor ◽  
Factor G

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.

scholarly journals Abnormal response to granulocyte colony-stimulating factor (G-CSF) in canine cyclic hematopoiesis is not caused by altered G-CSF receptor expression

Blood ◽  
1994 ◽  
Vol 84 (3) ◽  
pp. 789-794 ◽  
Author(s):  
BR Avalos ◽  
VC Broudy ◽  
SK Ceselski ◽  
BJ Druker ◽  
JD Griffin ◽  
...  
Keyword(s):  
Tyrosine Phosphorylation ◽  
Receptor Binding ◽  
Receptor Expression ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Cyclic Neutropenia ◽  
Abnormal Response ◽  
Cyclic Hematopoiesis ◽  
Stimulating Factor ◽  
Factor G

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.

Granulocyte-colony stimulating factor (G-CSF) and G-CSF receptor expression in human ischemic stroke

2006 ◽  
Vol 113 (1) ◽  
pp. 45-51 ◽  
Author(s):  
Martin Hasselblatt ◽  
Astrid Jeibmann ◽  
Barbara Riesmeier ◽  
David Maintz ◽  
Wolf-Rüdiger Schäbitz
Keyword(s):  
Ischemic Stroke ◽  
Receptor Expression ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Stimulating Factor ◽  
Factor G

Correction of canine cyclic hematopoiesis with recombinant human granulocyte colony-stimulating factor

Blood ◽  
1988 ◽  
Vol 72 (4) ◽  
pp. 1324-1328 ◽  
Author(s):  
CD Jr Lothrop ◽  
DJ Warren ◽  
LM Souza ◽  
JB Jones ◽  
MA Moore
Keyword(s):  
Neutralizing Antibodies ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Erythroid Progenitor ◽  
Cyclic Neutropenia ◽  
Biochemical Basis ◽  
Regulatory Defect ◽  
Wbc Count ◽  
Cyclic Hematopoiesis ◽  
Stimulating Factor

Abstract Canine cyclic hematopoiesis (CH) is an autosomal recessive disease of gray collie dogs that is characterized by neutropenic episodes at 14- day intervals. The biochemical basis for CH is not known but may involve a regulatory defect of the response to or production of a hematopoietic growth factor. Administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to two CH and one normal dog caused a marked leukocytosis (greater than 50,000 WBCs) in all three dogs. The leukocytosis was due largely to a greater than tenfold increase in neutrophils. Less pronounced but significant elevations in monocytes occurred during G-CSF treatment. The elevated WBC count was maintained for more than 20 days in all three dogs, and two predicted neutropenic episodes were prevented in both CH dogs during rhG-CSF treatment. A decline in the WBC count occurred simultaneously in all three dogs during the last five treatment days and was presumably associated with the development of neutralizing antibodies to the heterologous rhG-CSF protein. Bone marrow evaluation indicated that the swings in the myeloid/erythroid progenitor cells that are characteristic of CH were eliminated by rhG-CSF treatment in both CH dogs. These results suggest that the regulatory defect in canine CH can be temporarily alleviated by treatment with rhG-CSF and point to the potential treatment of human cyclic neutropenia with this agent.

scholarly journals Expression of receptors for granulocyte colony-stimulating factor on neutrophils from patients with severe congenital neutropenia and cyclic neutropenia

Blood ◽  
1992 ◽  
Vol 79 (5) ◽  
pp. 1144-1147 ◽  
Author(s):  
U Kyas ◽  
T Pietsch ◽  
K Welte
Keyword(s):  
Binding Sites ◽  
Signal Transduction Pathway ◽  
Receptor Expression ◽  
Scatchard Analysis ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Severe Congenital Neutropenia ◽  
Congenital Neutropenia ◽  
Cyclic Neutropenia ◽  
Stimulating Factor

Abstract We studied granulocyte colony-stimulating factor (G-CSF) binding sites on neutrophils from patients with severe congenital neutropenia (SCN; Kostmann-syndrome) and cyclic neutropenia (CN) during treatment with recombinant human (rh) G-CSF. G-CSF receptor expression was measured by scatchard analysis. Neutrophils from six healthy controls expressed between 480 and 1,210 binding sites per cell, whereas neutrophils from five SCN patients expressed increased numbers of G-CSF binding sites ranging between 2,100 and 3,900 per cell. Neutrophils from four patients with CN expressed 350 to 1,600 binding sites per cell. The affinity of rhG-CSF to its receptor was similar in patients and controls. These data suggest that SCN patients and CN patients are not defective in G-CSF receptor expression as judged by the numbers of G- CSF binding sites and binding affinity; however, we cannot exclude defects in parts of the G-CSF receptor that may be involved in the signal transduction pathway.

Expression of receptors for granulocyte colony-stimulating factor on neutrophils from patients with severe congenital neutropenia and cyclic neutropenia

Blood ◽  
1992 ◽  
Vol 79 (5) ◽  
pp. 1144-1147 ◽  
Author(s):  
U Kyas ◽  
T Pietsch ◽  
K Welte
Keyword(s):  
Binding Sites ◽  
Signal Transduction Pathway ◽  
Receptor Expression ◽  
Scatchard Analysis ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Severe Congenital Neutropenia ◽  
Congenital Neutropenia ◽  
Cyclic Neutropenia ◽  
Stimulating Factor

We studied granulocyte colony-stimulating factor (G-CSF) binding sites on neutrophils from patients with severe congenital neutropenia (SCN; Kostmann-syndrome) and cyclic neutropenia (CN) during treatment with recombinant human (rh) G-CSF. G-CSF receptor expression was measured by scatchard analysis. Neutrophils from six healthy controls expressed between 480 and 1,210 binding sites per cell, whereas neutrophils from five SCN patients expressed increased numbers of G-CSF binding sites ranging between 2,100 and 3,900 per cell. Neutrophils from four patients with CN expressed 350 to 1,600 binding sites per cell. The affinity of rhG-CSF to its receptor was similar in patients and controls. These data suggest that SCN patients and CN patients are not defective in G-CSF receptor expression as judged by the numbers of G- CSF binding sites and binding affinity; however, we cannot exclude defects in parts of the G-CSF receptor that may be involved in the signal transduction pathway.

scholarly journals Correction of canine cyclic hematopoiesis with recombinant human granulocyte colony-stimulating factor

Blood ◽  
1988 ◽  
Vol 72 (4) ◽  
pp. 1324-1328
Author(s):  
CD Jr Lothrop ◽  
DJ Warren ◽  
LM Souza ◽  
JB Jones ◽  
MA Moore
Keyword(s):  
Neutralizing Antibodies ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Erythroid Progenitor ◽  
Cyclic Neutropenia ◽  
Biochemical Basis ◽  
Regulatory Defect ◽  
Wbc Count ◽  
Cyclic Hematopoiesis ◽  
Stimulating Factor

Canine cyclic hematopoiesis (CH) is an autosomal recessive disease of gray collie dogs that is characterized by neutropenic episodes at 14- day intervals. The biochemical basis for CH is not known but may involve a regulatory defect of the response to or production of a hematopoietic growth factor. Administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to two CH and one normal dog caused a marked leukocytosis (greater than 50,000 WBCs) in all three dogs. The leukocytosis was due largely to a greater than tenfold increase in neutrophils. Less pronounced but significant elevations in monocytes occurred during G-CSF treatment. The elevated WBC count was maintained for more than 20 days in all three dogs, and two predicted neutropenic episodes were prevented in both CH dogs during rhG-CSF treatment. A decline in the WBC count occurred simultaneously in all three dogs during the last five treatment days and was presumably associated with the development of neutralizing antibodies to the heterologous rhG-CSF protein. Bone marrow evaluation indicated that the swings in the myeloid/erythroid progenitor cells that are characteristic of CH were eliminated by rhG-CSF treatment in both CH dogs. These results suggest that the regulatory defect in canine CH can be temporarily alleviated by treatment with rhG-CSF and point to the potential treatment of human cyclic neutropenia with this agent.

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