GM-CSF

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GM-CSF
GM-CSF
Model according to PDB  2GMF
Properties of human protein
Mass / length primary structure 127 amino acids
Secondary to quaternary structure Monomer
Identifier
Gene name CSF2
External IDs
Drug information
Drug class Immune stimulant
Occurrence
Parent taxon Mammals
Orthologue
human mouse
Entrez 1437 12981
Ensemble ENSG00000164400 ENSMUSG00000018916
UniProt P04141 P01587
Refseq (mRNA) NM_000758 NM_009969
Refseq (protein) NP_000749 NP_034099
Gene locus Chr 5: 132.07 - 132.08 Mb Chr 11: 54.25 - 54.25 Mb
PubMed search 1437 12981

The granulocyte-macrophage colony-stimulating factor or granulocyte-monocyte-colony-stimulating factor , GM-CSF for short (from English granulocyte-macrophage colony-stimulating factor ), is a glycoprotein that acts as a cytokine in mammals .

It is released into the blood by cells of the immune system and the endothelium in the body . In culture , it can cause the differentiation of bone marrow precursor cells into granulocytes and macrophages . In animals, differentiation into granulocytes and macrophages is possible even without GM-CSF, even if significantly fewer corresponding cells are formed.

GM-CSF is also part of the immune response to antigens and mitogens .

Apparently, GM-CSF as a T-cell cytokine is a necessary factor for the development of autoimmune inflammatory reactions such as those found in B. occur in multiple sclerosis . It also favors the migration of tissue-damaging phagocytes into the central nervous system .

Therapeutic and experimental use

Recombinantly produced human GM-CSF (rhGM-CSF) is used therapeutically to immune stimulation used.

Molgramostim , obtained biotechnologically from Escherichia coli strains, was used as Leucomax ( aH ) in the parenteral treatment of neutropenia , for example after radiotherapy . Because of the comparatively more favorable side effect profile, G-CSF preparations are more commonly used today. As Molgradex , Molgramostim is being developed for the inhalative treatment of alveolar proteinosis ( autoimmune pulmonary alveolar proteinosis , aPAP).

The glycosylated GM-CSF variant Sargramostim , produced using Saccharomyces cerevisiae strains, is approved in the USA as a leukine to accelerate hematological reconstitution after bone marrow transplantation and to treat neutropenia caused by cytostatic therapy of acute myeloid leukemia (AML). Another glycosylated rhGM-CSF is regramostim , which is obtained from CHO cells and has so far been used experimentally.

Dendritic cells for immunotherapy are usually obtained from monocytes of the patient by culture in GM-CSF and IL-4 . In combination immunotherapy , GM-CSF can be used together with immunizing agents.

In animal experiments it could be shown that a neutralization of GM-CSF prevents the outbreak of the experimental autoimmune encephalomyelitis (the animal model of multiple sclerosis) and can lead to healing in already sick animals. This neutralization process is being tested on people suffering from multiple sclerosis and rheumatoid arthritis (status 2011).

Both Molgramostim and Sargramostim are candidates for studies to investigate inhalation use to prevent the worsening of pneumonia and prevent acute lung failure in Covid-19 patients (as of August 2020).

Individual evidence

  1. ↑ Homologues at OMA
  2. ↑ GM-CSF murine rec. Retrieved July 27, 2020 .
  3. ↑ Kenneth Murphy, Casey Weaver: The Induced Responses of Innate Immunity . In: Janeway Immunology . Springer, Berlin, Heidelberg 2018, ISBN 978-3-662-56004-4 , pp. 155 , doi : 10.1007 / 978-3-662-56004-4_3 .
  4. ↑ Specialist knowledge of hematology oncology . Elsevier, 2020, ISBN 978-3-437-21215-4 , doi : 10.1016 / c2018-0-01275-x ( elsevier.com [accessed July 27, 2020]).
  5. ↑ W. Jelkmann: General properties of blood . In: Human physiology: with pathophysiology (=  Springer textbook ). Springer, Berlin, Heidelberg 2019, ISBN 978-3-662-56468-4 , pp. 296 , doi : 10.1007 / 978-3-662-56468-4_23 .
  6. ↑ Burkhard Becher, Sonia Tugues, Melanie Greter: GM-CSF: From Growth Factor to Central Mediator of Tissue Inflammation . In: Immunity . tape 45 , no. 5 , November 2016, p. 963–973 , doi : 10.1016 / j.immuni.2016.10.026 ( elsevier.com [accessed July 27, 2020]).
  7. ↑ Ian P. Wicks, Andrew W. Roberts: Targeting GM-CSF in inflammatory diseases . In: Nature Reviews Rheumatology . tape 12 , no. 1 , January 2016, ISSN  1759-4790 , p. 37–48 , doi : 10.1038 / nrrheum.2015.161 ( nature.com [accessed on July 27, 2020]).
  8. ↑ Laura Codarri, Gabor Gyülvészi, Vinko Tosevski, Lysann Hesske, Adriano Fontana: RORγt drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation . In: Nature Immunology . tape 12 , no. 6 , June 2011, ISSN  1529-2908 , p. 560-567 , doi : 10.1038 / ni.2027 ( nature.com [accessed July 27, 2020]).
  9. ↑ Hamilton JA, Anderson GP: GM-CSF Biology . In: Growth Factors . 22, No. 4, December 2004, pp. 225-31. doi : 10.1080 / 08977190412331279881 . PMID 15621725 .
  10. ↑ Hibbs ML, Quilici C, Kountouri N, Seymour JF, Armes JE, Burgess AW, Dunn AR: Mice lacking three myeloid colony-stimulating factors (G-CSF, GM-CSF, and M-CSF) still produce macrophages and granulocytes and mount an inflammatory response in a sterile model of peritonitis . In: J. Immunol . 178, No. 10, May 2007, pp. 6435-43. PMID 17475873 .
  11. ↑ External identifiers or database links to Molgramostim ( INN ) : CAS number: 99283-10-0, DrugBank : DB12525 , Wikidata : Q6896158 . UNII : B321AL142J . ATC code: L03 AA03
  12. ^ HC Schouten: Neutropenia management . Annals of Oncology, Volume 17 (2006), pp. 85-89, doi: 10.1093 / annonc / mdl243
  13. ↑ Savara Granted Breakthrough Therapy Designation for Molgradex for the Treatment of Autoimmune Pulmonary Alveolar Proteinosis (aPAP) , www.businesswire.com, December 30, 2029.
  14. ↑ External identifiers or database links to Sargramostim ( INN ) : CAS number: 123774-72-1 , DrugBank : DB00020 , Wikidata : Q3950557 . Other names: 23- L- Leucine-CSF 2 (human clone pHG 25 protein moiety). UNII : 5TAA004E22 . ATC code: L03 AA09
  15. ↑ Leukine, Prescribing Information on the FDA website ( PDF ), as of March 2018.
  16. ↑ External identifiers or database links to Regramostim ( INN ) : CAS number: 127757-91-9, DrugBank : DB05386 . Other names: Human clone PCSF-1 protein moiety reduced, glycoform GMC 89-107. UNII : KR89Q40F01 .
  17. ↑ Tawab A, Fan Y, Read EJ, Kurlander RJ: Effect of ex vivo culture duration on phenotype and cytokine production by mature dendritic cells derived from peripheral blood monocytes . In: transfusion . 49, No. 3, March 2009, pp. 536-47. doi : 10.1111 / j.1537-2995.2008.02020.x . PMID 19243546 .
  18. ↑ Seo SH, Han HD, Noh KH, Kim TW, Son SW: Chitosan hydrogel containing GMCSF and a cancer drug exerts synergistic anti-tumor effects via the induction of CD8 + T cell-mediated anti-tumor immunity . In: Clin. Exp. Metastasis . 26, No. 3, 2009, pp. 179-87. doi : 10.1007 / s10585-008-9228-5 . PMID 19082918 .
  19. ↑ Fong L, Kwek SS, O'Brien S, et al. : Potentiating endogenous antitumor immunity to prostate cancer through combination immunotherapy with CTLA4 blockade and GM-CSF . In: Cancer Res . 69, No. 2, January 2009, pp. 609-15. doi : 10.1158 / 0008-5472.CAN-08-3529 . PMID 19147575 .
  20. ↑ Codarri, L., Gyülveszi, G., Magnenat, L., Hesske, L., Fontana, A., Suter, T., Becher, B .: RORgt drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation . In: Nature Immunology . April 2011. doi : 10.1038 / ni.2027 . PMID 21516112 .
  21. ↑ "GM-CSF is needed for immune attacks in multiple sclerosis" from journalmed.de - accessed on May 1, 2011
  22. ↑ S. Siebenand: molgramostim inhalation in heavy Covid-19 course , Pharmaceutical newspaper, August 7 2020th