Granulocyte-macrophage colony-stimulating factor: Difference between revisions
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'''Granulocyte-macrophage colony-stimulating factor''' ('''GM-CSF'''), also known as '''colony-stimulating factor 2 (CSF2)''', is a [[monomeric]] [[glycoprotein]] secreted by [[macrophage]]s, [[T cell]]s, [[mast cells]], [[natural killer cell]]s, [[endothelial cell]]s and [[fibroblast]]s that functions as a [[cytokine]]. The [[pharmaceutical drug|pharmaceutical]] analogs of naturally occurring GM-CSF are called [[sargramostim]] and [[molgramostim]]. |
'''Granulocyte-macrophage colony-stimulating factor''' ('''GM-CSF'''), also known as '''colony-stimulating factor 2 (CSF2)''', is a [[monomeric]] [[glycoprotein]] secreted by [[macrophage]]s, [[T cell]]s, [[mast cells]], [[natural killer cell]]s, [[endothelial cell]]s and [[fibroblast]]s that functions as a [[cytokine]]. The [[pharmaceutical drug|pharmaceutical]] analogs of naturally occurring GM-CSF are called [[sargramostim]] and [[molgramostim]]. |
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Unlike [[granulocyte colony-stimulating factor]], which specifically promotes [[neutrophil]] proliferation and maturation, GM-CSF affects more cell types, especially macrophages and [[eosinophil]]s.<ref name="pmid10081506">{{cite journal | vauthors=Root RK, Dale DC | title=Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor: comparisons and potential for use in the treatment of infections in nonneutropenic patients| journal= |
Unlike [[granulocyte colony-stimulating factor]], which specifically promotes [[neutrophil]] proliferation and maturation, GM-CSF affects more cell types, especially macrophages and [[eosinophil]]s.<ref name="pmid10081506">{{cite journal | vauthors = Root RK, Dale DC | title = Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor: comparisons and potential for use in the treatment of infections in nonneutropenic patients | journal = The Journal of Infectious Diseases | volume = 179 Suppl 2 | issue = Suppl 2 | pages = S342-52 | date = March 1999 | pmid = 10081506 | doi = 10.1086/513857 }}</ref> |
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== Function == |
== Function == |
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GM-CSF is a [[monomeric]] [[glycoprotein]] that functions as a [[cytokine]] — it is a [[white blood cell]] [[growth factor]].<ref name="pmid24264600">{{cite journal | vauthors = Francisco-Cruz A, Aguilar-Santelises M, Ramos-Espinosa O, Mata-Espinosa D, Marquina-Castillo B, Barrios-Payan J, Hernandez-Pando R | title = Granulocyte-macrophage colony-stimulating factor: not just another haematopoietic growth factor | journal = Medical Oncology | volume = 31 | issue = 1 | pages = 774 | date = |
GM-CSF is a [[monomeric]] [[glycoprotein]] that functions as a [[cytokine]] — it is a [[white blood cell]] [[growth factor]].<ref name="pmid24264600">{{cite journal | vauthors = Francisco-Cruz A, Aguilar-Santelises M, Ramos-Espinosa O, Mata-Espinosa D, Marquina-Castillo B, Barrios-Payan J, Hernandez-Pando R | title = Granulocyte-macrophage colony-stimulating factor: not just another haematopoietic growth factor | journal = Medical Oncology | volume = 31 | issue = 1 | pages = 774 | date = January 2014 | pmid = 24264600 | doi = 10.1007/s12032-013-0774-6 }}</ref> GM-CSF stimulates [[stem cell]]s to produce [[granulocyte]]s ([[neutrophil]]s, [[eosinophil]]s, and [[basophil]]s) and [[monocyte]]s. Monocytes exit the circulation and migrate into tissue, whereupon they mature into [[macrophage]]s and [[dendritic cell]]s. Thus, it is part of the [[immune system|immune]]/[[inflammation|inflammatory]] [[biochemical cascade|cascade]], by which activation of a small number of macrophages can rapidly lead to an increase in their numbers, a process crucial for fighting [[infection]]. |
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GM-CSF also has some effects on mature cells of the immune system. These include, for example, inhibiting neutrophil migration and causing an alteration of the receptors expressed on the cells surface.<ref>{{cite journal | vauthors = Gasson JC | title = Molecular physiology of granulocyte-macrophage colony-stimulating factor | journal = Blood | volume = 77 | issue = 6 | pages = 1131–45 | date = |
GM-CSF also has some effects on mature cells of the immune system. These include, for example, inhibiting neutrophil migration and causing an alteration of the receptors expressed on the cells surface.<ref>{{cite journal | vauthors = Gasson JC | title = Molecular physiology of granulocyte-macrophage colony-stimulating factor | journal = Blood | volume = 77 | issue = 6 | pages = 1131–45 | date = March 1991 | pmid = 2001448 | url = http://www.bloodjournal.org/content/77/6/1131 }}</ref> |
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GM-CSF signals via signal transducer and activator of transcription, [[STAT5]].<ref name="pmid23042651">{{cite journal | vauthors = Voehringer D | title = Basophil modulation by cytokine instruction | journal = European Journal of Immunology | volume = 42 | issue = 10 | pages = 2544–50 | date = |
GM-CSF signals via signal transducer and activator of transcription, [[STAT5]].<ref name="pmid23042651">{{cite journal | vauthors = Voehringer D | title = Basophil modulation by cytokine instruction | journal = European Journal of Immunology | volume = 42 | issue = 10 | pages = 2544–50 | date = October 2012 | pmid = 23042651 | doi = 10.1002/eji.201142318 }}</ref> In macrophages, it has also been shown to signal via [[STAT3]]. The cytokine activates macrophages to inhibit fungal survival. It induces deprivation in intracellular free zinc and increases production of [[reactive oxygen species]] that culminate in fungal zinc starvation and toxicity.<ref name="pmid24138881">{{cite journal | vauthors = Subramanian Vignesh K, Landero Figueroa JA, Porollo A, Caruso JA, Deepe GS | title = Granulocyte macrophage-colony stimulating factor induced Zn sequestration enhances macrophage superoxide and limits intracellular pathogen survival | journal = Immunity | volume = 39 | issue = 4 | pages = 697–710 | date = October 2013 | pmid = 24138881 | pmc = 3841917 | doi = 10.1016/j.immuni.2013.09.006 }}</ref> Thus, GM-CSF facilitates development of the immune system and promotes defense against infections. |
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GM-CSF also plays a role in embryonic development by functioning as an [[embryokine]] produced by reproductive tract.<ref name="pmid24954585">{{cite journal | vauthors = Hansen PJ, Dobbs KB, Denicol AC | title = Programming of the preimplantation embryo by the embryokine colony stimulating factor 2 | journal = Animal Reproduction Science | volume = 149 | issue = |
GM-CSF also plays a role in embryonic development by functioning as an [[embryokine]] produced by reproductive tract.<ref name="pmid24954585">{{cite journal | vauthors = Hansen PJ, Dobbs KB, Denicol AC | title = Programming of the preimplantation embryo by the embryokine colony stimulating factor 2 | journal = Animal Reproduction Science | volume = 149 | issue = 1-2 | pages = 59–66 | date = September 2014 | pmid = 24954585 | doi = 10.1016/j.anireprosci.2014.05.017 }}</ref> |
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== Genetics == |
== Genetics == |
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The human gene has been localized in close proximity to the [[interleukin 3]] gene within a [[T helper cell|T helper]] type 2-associated cytokine gene cluster at chromosome region 5q31, which is known to be associated with interstitial deletions in the [[5q- syndrome]] and [[acute myelogenous leukemia]]. GM-CSF and IL-3 are separated by an insulator element and thus independently regulated.<ref name=" |
The human gene has been localized in close proximity to the [[interleukin 3]] gene within a [[T helper cell|T helper]] type 2-associated cytokine gene cluster at chromosome region 5q31, which is known to be associated with interstitial deletions in the [[5q- syndrome]] and [[acute myelogenous leukemia]]. GM-CSF and IL-3 are separated by an insulator element and thus independently regulated.<ref name="pmid19158269">{{cite journal | vauthors = Bowers SR, Mirabella F, Calero-Nieto FJ, Valeaux S, Hadjur S, Baxter EW, Merkenschlager M, Cockerill PN | title = A conserved insulator that recruits CTCF and cohesin exists between the closely related but divergently regulated interleukin-3 and granulocyte-macrophage colony-stimulating factor genes | journal = Molecular and Cellular Biology | volume = 29 | issue = 7 | pages = 1682–93 | date = April 2009 | pmid = 19158269 | pmc = 2655614 | doi = 10.1128/MCB.01411-08 }}</ref> Other genes in the cluster include those encoding [[Interleukin 4|interleukins 4]], [[Interleukin 5|5]], and [[Interleukin 13|13]].<ref>{{cite web | title = Entrez Gene: CSF2 colony stimulating factor 2 (granulocyte-macrophage) | url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1437 }}</ref> |
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== Glycosylation == |
== Glycosylation == |
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== Medical use == |
== Medical use == |
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GM-CSF was first cloned in the 1985, and soon afterwards three potential drug products were being made using [[recombinant DNA]] technology: [[molgramostim]] was made in ''Escherichia coli'' and is not glycosylated, [[sargramostim]] was made in yeast, has a leucine instead of proline at position 23 and is somewhat glyocylated, and [[regramostim]] was made in Chinese hamster ovary cells (CHO) and has more glycosylation than sargramostim. The amount of glycosylation affects how the body interacts with the drug and how the drug interacts with the body.<ref>{{cite journal| |
GM-CSF was first cloned in the 1985, and soon afterwards three potential drug products were being made using [[recombinant DNA]] technology: [[molgramostim]] was made in ''Escherichia coli'' and is not glycosylated, [[sargramostim]] was made in yeast, has a leucine instead of proline at position 23 and is somewhat glyocylated, and [[regramostim]] was made in Chinese hamster ovary cells (CHO) and has more glycosylation than sargramostim. The amount of glycosylation affects how the body interacts with the drug and how the drug interacts with the body.<ref>{{cite journal | vauthors = Armitage JO | title = Emerging applications of recombinant human granulocyte-macrophage colony-stimulating factor | journal = Blood | volume = 92 | issue = 12 | pages = 4491–508 | date = December 1998 | pmid = 9845514 | url = http://www.bloodjournal.org/content/bloodjournal/92/12/4491.full.pdf?sso-checked=true }}</ref> |
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At that time, [[Genetics Institute, Inc.]] was working on molgramostim,<ref>{{cite web|title=Molgramostim|url=https://adisinsight.springer.com/drugs/800004167|publisher=AdisInsight| |
At that time, [[Genetics Institute, Inc.]] was working on molgramostim,<ref>{{cite web|title=Molgramostim|url=https://adisinsight.springer.com/drugs/800004167|publisher=AdisInsight|access-date=3 April 2018|language=en}}</ref> [[Immunex]] was working on [[sargramostim]] (Leukine),<ref name=back>{{cite journal|last1=Staff|title=Back to the Future: Original Liquid Leukine® Coming Soon|journal=Oncology Business Review|date=May 2008|url=https://obroncology.com/documents/OBR_may08_LEUKINE.pdf}}</ref> and [[Sandoz]] was working on regramostim.<ref>{{cite journal | vauthors = Hussein AM, Ross M, Vredenburgh J, Meisenberg B, Hars V, Gilbert C, Petros WP, Coniglio D, Kurtzberg J, Rubin P | title = Effects of granulocyte-macrophage colony stimulating factor produced in Chinese hamster ovary cells (regramostim), Escherichia coli (molgramostim) and yeast (sargramostim) on priming peripheral blood progenitor cells for use with autologous bone marrow after high-dose chemotherapy | journal = European Journal of Haematology | volume = 55 | issue = 5 | pages = 348–56 | date = November 1995 | pmid = 7493686 }}</ref> |
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Molgramostim was eventually co-developed and co-marketed by Novartis and Schering-Plough under the trade name Leucomax for use in helping white blood cell levels recover following chemotherapy, and in 2002 Novartis sold its rights to Schering-Plough.<ref>{{cite web|title=Press release: Novartis Oncology sharpens focus on key growth drivers|url=https://www.sec.gov/Archives/edgar/data/1114448/000091205702040732/a2092547z6-k.htm|publisher=Novartis via SEC Edgar|date=30 October 2002}}</ref><ref>{{cite web|title=Scientific Conclusions and Grounds for Amendment of the Summary of Product Characteristics Presented by the EMEA|url=http://ec.europa.eu/health/documents/community-register/2000/200006273658/anx_3658_en.pdf|publisher=EMA CPMP|date=27 June 2000}}</ref> |
Molgramostim was eventually co-developed and co-marketed by Novartis and Schering-Plough under the trade name Leucomax for use in helping white blood cell levels recover following chemotherapy, and in 2002 Novartis sold its rights to Schering-Plough.<ref>{{cite web|title=Press release: Novartis Oncology sharpens focus on key growth drivers|url=https://www.sec.gov/Archives/edgar/data/1114448/000091205702040732/a2092547z6-k.htm|publisher=Novartis via SEC Edgar|date=30 October 2002}}</ref><ref>{{cite web|title=Scientific Conclusions and Grounds for Amendment of the Summary of Product Characteristics Presented by the EMEA|url=http://ec.europa.eu/health/documents/community-register/2000/200006273658/anx_3658_en.pdf|publisher=EMA CPMP|date=27 June 2000}}</ref> |
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Sargramostim was approved by the US FDA in 1991 to accelerate white blood cell recovery following autologous [[bone marrow transplantation]] under the trade name Leukine, and passed through several hands, ending up with [[Genzyme]]<ref>{{cite web |url=http://www.pharmaceutical-technology.com/projects/berlex/ |title=Bayer Healthcare Pharmaceuticals Plant, Snohomish County, Washington State |author= |work= |publisher=pharmaceutical-technology.com | |
Sargramostim was approved by the US FDA in 1991 to accelerate white blood cell recovery following autologous [[bone marrow transplantation]] under the trade name Leukine, and passed through several hands, ending up with [[Genzyme]]<ref>{{cite web |url=http://www.pharmaceutical-technology.com/projects/berlex/ |title=Bayer Healthcare Pharmaceuticals Plant, Snohomish County, Washington State |author= |work= |publisher=pharmaceutical-technology.com |access-date=12 November 2011}}</ref> which subsequently was acquired by [[Sanofi]]. |
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==Research directions== |
==Research directions== |
||
GM-CSF is found in high levels in joints with [[rheumatoid arthritis]] and blocking GM-CSF as a [[biological target]] may reduce the inflammation or damage. Some drugs (e.g. [[MOR103]]) are being developed to ''block'' GM-CSF.<ref name="pmid23448220">{{cite journal | vauthors = Deiß A, Brecht I, Haarmann A, Buttmann M | title = Treating multiple sclerosis with monoclonal antibodies: a 2013 update | journal = Expert Review of Neurotherapeutics | volume = 13 | issue = 3 | pages = 313–35 | date = |
GM-CSF is found in high levels in joints with [[rheumatoid arthritis]] and blocking GM-CSF as a [[biological target]] may reduce the inflammation or damage. Some drugs (e.g. [[MOR103]]) are being developed to ''block'' GM-CSF.<ref name="pmid23448220">{{cite journal | vauthors = Deiß A, Brecht I, Haarmann A, Buttmann M | title = Treating multiple sclerosis with monoclonal antibodies: a 2013 update | journal = Expert Review of Neurotherapeutics | volume = 13 | issue = 3 | pages = 313–35 | date = March 2013 | pmid = 23448220 | doi = 10.1586/ern.13.17 }}</ref> |
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== See also == |
== See also == |
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== References == |
== References == |
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{{Reflist| |
{{Reflist|32em}} |
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== External links == |
== External links == |
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Revision as of 02:41, 3 April 2018
| Granulocyte-macrophage colony-stimulating factor | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 three-dimensional structure of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM_CSF) | |||||||||
| Identifiers | |||||||||
| Symbol | GM_CSF | ||||||||
| Pfam | PF01109 | ||||||||
| Pfam clan | CL0053 | ||||||||
| InterPro | IPR000773 | ||||||||
| PROSITE | PDOC00584 | ||||||||
| SCOP2 | 2gmf / SCOPe / SUPFAM | ||||||||
| |||||||||
 | |
| Clinical data | |
|---|---|
| ATC code | |
| Identifiers | |
| |
| CAS Number | |
| DrugBank | |
| ChemSpider |
|
| Chemical and physical data | |
| Formula | C639H1006N168O196S8 |
| Molar mass | 14434.5 g/mol g·mol−1 |
  (what is this?) (verify) | |
Granulocyte-macrophage colony-stimulating factor (GM-CSF), also known as colony-stimulating factor 2 (CSF2), is a monomeric glycoprotein secreted by macrophages, T cells, mast cells, natural killer cells, endothelial cells and fibroblasts that functions as a cytokine. The pharmaceutical analogs of naturally occurring GM-CSF are called sargramostim and molgramostim.
Unlike granulocyte colony-stimulating factor, which specifically promotes neutrophil proliferation and maturation, GM-CSF affects more cell types, especially macrophages and eosinophils.[5]
Function
GM-CSF is a monomeric glycoprotein that functions as a cytokine — it is a white blood cell growth factor.[6] GM-CSF stimulates stem cells to produce granulocytes (neutrophils, eosinophils, and basophils) and monocytes. Monocytes exit the circulation and migrate into tissue, whereupon they mature into macrophages and dendritic cells. Thus, it is part of the immune/inflammatory cascade, by which activation of a small number of macrophages can rapidly lead to an increase in their numbers, a process crucial for fighting infection.
GM-CSF also has some effects on mature cells of the immune system. These include, for example, inhibiting neutrophil migration and causing an alteration of the receptors expressed on the cells surface.[7]
GM-CSF signals via signal transducer and activator of transcription, STAT5.[8] In macrophages, it has also been shown to signal via STAT3. The cytokine activates macrophages to inhibit fungal survival. It induces deprivation in intracellular free zinc and increases production of reactive oxygen species that culminate in fungal zinc starvation and toxicity.[9] Thus, GM-CSF facilitates development of the immune system and promotes defense against infections.
GM-CSF also plays a role in embryonic development by functioning as an embryokine produced by reproductive tract.[10]
Genetics
The human gene has been localized in close proximity to the interleukin 3 gene within a T helper type 2-associated cytokine gene cluster at chromosome region 5q31, which is known to be associated with interstitial deletions in the 5q- syndrome and acute myelogenous leukemia. GM-CSF and IL-3 are separated by an insulator element and thus independently regulated.[11] Other genes in the cluster include those encoding interleukins 4, 5, and 13.[12]
Glycosylation
Human granulocyte-macrophage colony-stimulating factor is glycosylated in its mature form.
Medical use
GM-CSF was first cloned in the 1985, and soon afterwards three potential drug products were being made using recombinant DNA technology: molgramostim was made in Escherichia coli and is not glycosylated, sargramostim was made in yeast, has a leucine instead of proline at position 23 and is somewhat glyocylated, and regramostim was made in Chinese hamster ovary cells (CHO) and has more glycosylation than sargramostim. The amount of glycosylation affects how the body interacts with the drug and how the drug interacts with the body.[13]
At that time, Genetics Institute, Inc. was working on molgramostim,[14] Immunex was working on sargramostim (Leukine),[15] and Sandoz was working on regramostim.[16]
Molgramostim was eventually co-developed and co-marketed by Novartis and Schering-Plough under the trade name Leucomax for use in helping white blood cell levels recover following chemotherapy, and in 2002 Novartis sold its rights to Schering-Plough.[17][18]
Sargramostim was approved by the US FDA in 1991 to accelerate white blood cell recovery following autologous bone marrow transplantation under the trade name Leukine, and passed through several hands, ending up with Genzyme[19] which subsequently was acquired by Sanofi.
Research directions
GM-CSF is found in high levels in joints with rheumatoid arthritis and blocking GM-CSF as a biological target may reduce the inflammation or damage. Some drugs (e.g. MOR103) are being developed to block GM-CSF.[20]
See also
- CFU-GM
- Granulocyte-macrophage colony-stimulating factor receptor
- Filgrastim (Neupogen, a granulocyte colony-stimulating factor (G-CSF) analog)
- Pegfilgrastim (Neulasta, a PEGylated form filgrastim)
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000164400 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000018916 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Root RK, Dale DC (March 1999). "Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor: comparisons and potential for use in the treatment of infections in nonneutropenic patients". The Journal of Infectious Diseases. 179 Suppl 2 (Suppl 2): S342-52. doi:10.1086/513857. PMID 10081506.
- ^ Francisco-Cruz A, Aguilar-Santelises M, Ramos-Espinosa O, Mata-Espinosa D, Marquina-Castillo B, Barrios-Payan J, Hernandez-Pando R (January 2014). "Granulocyte-macrophage colony-stimulating factor: not just another haematopoietic growth factor". Medical Oncology. 31 (1): 774. doi:10.1007/s12032-013-0774-6. PMID 24264600.
- ^ Gasson JC (March 1991). "Molecular physiology of granulocyte-macrophage colony-stimulating factor". Blood. 77 (6): 1131–45. PMID 2001448.
- ^ Voehringer D (October 2012). "Basophil modulation by cytokine instruction". European Journal of Immunology. 42 (10): 2544–50. doi:10.1002/eji.201142318. PMID 23042651.
- ^ Subramanian Vignesh K, Landero Figueroa JA, Porollo A, Caruso JA, Deepe GS (October 2013). "Granulocyte macrophage-colony stimulating factor induced Zn sequestration enhances macrophage superoxide and limits intracellular pathogen survival". Immunity. 39 (4): 697–710. doi:10.1016/j.immuni.2013.09.006. PMC 3841917. PMID 24138881.
- ^ Hansen PJ, Dobbs KB, Denicol AC (September 2014). "Programming of the preimplantation embryo by the embryokine colony stimulating factor 2". Animal Reproduction Science. 149 (1–2): 59–66. doi:10.1016/j.anireprosci.2014.05.017. PMID 24954585.
- ^ Bowers SR, Mirabella F, Calero-Nieto FJ, Valeaux S, Hadjur S, Baxter EW, Merkenschlager M, Cockerill PN (April 2009). "A conserved insulator that recruits CTCF and cohesin exists between the closely related but divergently regulated interleukin-3 and granulocyte-macrophage colony-stimulating factor genes". Molecular and Cellular Biology. 29 (7): 1682–93. doi:10.1128/MCB.01411-08. PMC 2655614. PMID 19158269.
- ^ "Entrez Gene: CSF2 colony stimulating factor 2 (granulocyte-macrophage)".
- ^ Armitage JO (December 1998). "Emerging applications of recombinant human granulocyte-macrophage colony-stimulating factor" (PDF). Blood. 92 (12): 4491–508. PMID 9845514.
- ^ "Molgramostim". AdisInsight. Retrieved 3 April 2018.
- ^ Staff (May 2008). "Back to the Future: Original Liquid Leukine® Coming Soon" (PDF). Oncology Business Review.
- ^ Hussein AM, Ross M, Vredenburgh J, Meisenberg B, Hars V, Gilbert C, Petros WP, Coniglio D, Kurtzberg J, Rubin P (November 1995). "Effects of granulocyte-macrophage colony stimulating factor produced in Chinese hamster ovary cells (regramostim), Escherichia coli (molgramostim) and yeast (sargramostim) on priming peripheral blood progenitor cells for use with autologous bone marrow after high-dose chemotherapy". European Journal of Haematology. 55 (5): 348–56. PMID 7493686.
- ^ "Press release: Novartis Oncology sharpens focus on key growth drivers". Novartis via SEC Edgar. 30 October 2002.
- ^ "Scientific Conclusions and Grounds for Amendment of the Summary of Product Characteristics Presented by the EMEA" (PDF). EMA CPMP. 27 June 2000.
- ^ "Bayer Healthcare Pharmaceuticals Plant, Snohomish County, Washington State". pharmaceutical-technology.com. Retrieved 12 November 2011.
- ^ Deiß A, Brecht I, Haarmann A, Buttmann M (March 2013). "Treating multiple sclerosis with monoclonal antibodies: a 2013 update". Expert Review of Neurotherapeutics. 13 (3): 313–35. doi:10.1586/ern.13.17. PMID 23448220.
External links
- Official gentaur web site
- Official Leukine web site
- Granulocyte-Macrophage+Colony-Stimulating+Factor at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
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