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0032 (0)16 41 44 07
+32 1650 9045
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Česká republika Praha
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0032 (0)16 41 44 07
Pegylated Recombinant Human Granulocyte-Colony Stimulating Factor (PEG-GCSF)
(Cat. No.: C028)
A glycoprotein of MW 20 kDa containing internal disulfide bonds. It induces the survival, proliferation, and differentiation of neutrophilic granulocyte precursor cells and functionally activates mature blood neutrophils. Among the family of colony-stimulating factors, G-CSF is the most potent inducer of terminal differentiation to granulocytes and macrophages of leukemic myeloid cell lines.
The synthesis of G-CSF can be induced by bacterial endotoxins, TNF, IL-1 and GM-CSF. Prostaglandin E2 inhibits the synthesis of G-CSF. In epithelial, endothelial, and fibroblastic cells secretion of G-CSF is induced by IL-17.
Recombinant Human G-CSF produced in E. coli is a single, non-glycosylated, polypeptide chain containing 175 amino acids and having a molecular mass of 18,800 Dalton. PEG-GCSF is manufactured by attaching a 20,000 Dalton methoxypolyethylene glycol propionaldehyde (mPEG-ALD) to the N-terminal amino acid of G-CSF having a total molecular mass of 38,800 Dalton.
Biological Activity: PEG-GCSF is fully biologically active when compared to standard. The ED50, calculated by the dose-dependant proliferation of murine NFS-60 indicator cells is less then 0.1 ng/ml, corresponding to a Specific Activity of 1.0 x 107 IU/mg.
Purity: Greater than 95% as determined by:
(a) Analysis by HPLC.
(b) Anion-exchange FPLC.
(c) Analysis by reducing and non-reducing SDS-PAGE Silver Stained gel.
Amino acid sequence: The sequence of the first five N-terminal amino acids was determined and was found to be Met-Thr-Pro-Leu-Gly.
Endotoxin: Less than 0.1 ng/µg (1IEU/µg) of PEG-GCSF.
Formulation: The protein was extensively dialyzed against 10mM sodium acetate buffer PH= 4 and 5% mannitol was added.
Storage: PEG-GCSF although stable at 15oC for 1 week, should be stored between 2oC -8oC. For long-term storage it is recommended to add a carrier protein (0.1% HSA or BSA).
Please avoid freeze-thaw cycles.
Reconstitution: It is recommended to reconstitute the lyophilized PEG-GCSF in sterile 18MΩ-cm H2O not less than 100µg/ml, which can then be further diluted to other aqueous solutions.
1: Bull Exp Biol Med 2008 May;Vol 145(5)
Delayed effects of long-term administration of granulocyte colony-stimulating factor to mice.
[Abstract] We studied the effects of chronic administration of granulocyte colony-stimulating factor in nonmobilizing doses to mice. Over 18 months of the study, 55% animals of the treatment group died of unknown cause, blood diseases and tumors were found in 20% mice, and in 5% animals pathological changes were absent. Control mice had no diseases (normal values of total and differential leukocyte count). The diagnoses made over the first 7 months mainly included myeloproliferative diseases. Solid tumors were found at later terms. Suppurative inflammation at the site of injection was observed in all mice after 3-month treatment with granulocyte colony-stimulating factor. Our results indicate that chronic administration of granulocyte colony-stimulating factor in low
doses leads to the development of etiologically different tumors and sharply reduced animal life span. The use of granulocyte colony-stimulating factor during allogeneic transplantation of hemopoietic stem cells can be hazardous for donors.
2: Cardiovasc Pathol 2009
Effects of granulocyte-colony stimulating factor on bone marrow-derived progenitor cells in murine cardiac transplantation.
3: Blood 2009 Jan;
Zebrafish granulocyte colony-stimulating factor receptor signaling promotes myelopoiesis and myeloid cell migration.
[Abstract] Granulocyte colony-stimulating factor receptor (GCSFR) signaling participates in the production of neutrophilic granulocytes during normal hematopoietic development, with a particularly important role during emergency hematopoiesis. This study describes the characterization of the zebrafish gcsf and gcsfr genes, which showed broad conservation and similar regulation to their mammalian counterparts. Morpholino-mediated knockdown of gcsfr and overexpression of gcsf revealed the presence of an anterior population of myeloid cells during primitive hematopoiesis that were dependent on GCSF/GCSFR for their development and migration. This contrasted with a posterior domain that was largely independent of this pathway. Definitive myelopoiesis was also partially
dependent on a functional GCSF/GCSFR pathway. Injection of bacterial lipopolysaccharide elicited significant induction of gcsf expression and emergency production of myeloid cells, which was abrogated by gcsfr knockdown. Collectively, these data demonstrate GCSF/GCSFR to be a conserved signaling system for facilitating the production of multiple myeloid cell lineages in both homeostatic and emergency conditions, as well as for early myeloid cell migration, establishing a useful experimental platform for further dissection of this pathway.
4: Am J Physiol Heart Circ Physiol 2009
Granulocyte colony-stimulating factor protects cardiac mitochondria in the early phase of cardiac injury.
[Abstract] Although granulocyte colony-stimulating factor (G-CSF) reportedly plays a cardioprotective role in several models of cardiac injury, clinical use of this drug for cardiac patients has been controversial. Here, we tested the effect of G-CSF in vivo and in vitro on cardiac mitochondria, which play a key role in determining cardiac cellular fate and function. Mild stimulation of C57/BL6 mice with doxorubicin (dox)did not induce cardiac apoptosis or fibrosis, but did induce electron microscopic damages in the mitochondrial alignment of the myocardium. Cardiac catheterization or echocardiogram revealed that dox did not alter cardiac systolic function or left ventricular size, but did reduce diastolic function, an early sign of cardiac damage. Treatment with G-CSF
significantly rescued both cardiac mitochondrial changes and diastolic function. In an in vitro model with rat neonatal cardiomyocytes, a sub-apoptotic dose of dox induced severe mitochondrial damage, including markedly swelling of the cardiac mitochondria and/or decreased mitochondrial membrane potential. These mitochondrial changes were completely avoided by pretreatment with G-CSF. In addition, G-CSF dramatically improved ATP generation, rescuing dox-impaired mitochondrial electron transport and oxygen consumption, which was mainly through Complex IV. These findings clearly indicate that G-CSF protects cardiac mitochondria, key organelles in determining cardiac cellular fate, in the early phase of cardiac injury. Key words: G-CSF, mitochondria, oxygen consumption, doxorubicin, cardiac
Protein Accession No.:
MTPLG PASSL PQSFL LKCLE QVRKI QGDGA ALQEK LCATY KLCHP EELVL LGHSL GIPWA PLSSC PSQAL QLAGC LSQLH SGLFL YQGLL QALEG ISPEL GPTLD TLQLD VADFA TTIWQ QMEEL GMAPA LQPTQ GAMPA FASAF QRRAG GVLVA SHLQS FLEVS YRVLR HLAQP
*NOTE: ALL PRODUCTS ARE FOR RESEARCH USE ONLY