- 同？
- リポ多糖受容体 LPS受容体 lipopolysaccharide receptor, LPS receptor
LPSの受容 (SMB.117)
- LPSはマクロファージ、単球、顆粒球、Bリンパ球と反応し、多彩な生物活性を発現する。この反応には細胞表面のToll-like receptor。TLR-4がLPSのレセブタ-としてはたらき, LPSのシグナルを細胞内へと伝達する。このTLR-4の機能不全はLPSに対する応答性を失わせる。 TLR-4のほかに, CD14やMD-2と呼ばれる分子もLPSの認識に関与している。このTLRは分子群を形成し,ペプチドグリカン,リポタンパク質DNAなどの菌体成分を認識し,感染防御に重要なシグナルを伝達する。
発現細胞
機能
PrepTutorEJDIC
- certificate of deposit / (また『C.D.』)Civil Defense民間防衛
Wikipedia preview
出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/11/14 17:00:37」(JST)
[Wiki ja表示]
CD14 はヒトやマウスなどにみられる遺伝子、もしくはそれがコードするタンパク質である[1][2]。
CD14タンパク質は自然免疫系の構成要素の一つである。CD14は2種類の形態を取り得る。1つはグリコシルホスファチジルイノシトールアンカーによって細胞膜上に固定された膜貫通型タンパク質で (mCD14) 、もう1つは可溶性タンパク質である (sCD14) 。sCD14はmCD14の細胞膜からの脱落 (48 kDa) 、あるいは細胞内輸送によって直接分泌されることによって生じる (56 kDa) [3] 。
X線結晶構造解析により、CD14の構造が明らかになった。これによると、CD14は単量体の折れ曲がったコイル状の構造を持ち、アミノ末端には疎水性のポケットを持つ[4] 。
CD14は最初に発見されたパターン認識受容体でもある。
目次
- 1 機能
- 2 組織分布
- 3 脚注
- 4 外部リンク
- 5 参考文献
機能
CD14は共受容体として（TLR4あるいはMD-2と共に）働き、細菌に由来するリポ多糖 (LPS) を認識する[5][6]。CD14とLPSの結合はリポ多糖結合タンパク質 (LBP) に依存し、LBPの存在下でのみCD14とTLR4はLPSと結合しうる。LPSはCD14の主要なリガンドであるが、CD14は他にも細菌由来の病原体関連分子パターンを認識することができる[7] 。
また、CD14はTLR4のみならずTLR2やTLR3のリガンド結合にも関わる[8]。
TLRのシグナル経路。灰色の点線は未知の経路を示す。
組織分布
CD14は単球、マクロファージ、顆粒球などの骨髄系細胞に発現している[8]。
脚注
- ^ Setoguchi M, Nasu N, Yoshida S, Higuchi Y, Akizuki S, Yamamoto S (July 1989). "Mouse and human CD14 (myeloid cell-specific leucine-rich glycoprotein) primary structure deduced from cDNA clones". Biochim. Biophys. Acta 1008 (2): 213–22. doi:10.1016/0167-4781(80)90012-3. PMID 2472171.
- ^ Simmons DL, Tan S, Tenen DG, Nicholson-Weller A, Seed B (1 January 1989). "Monocyte antigen CD14 is a phospholipid anchored membrane protein". Blood 73 (1): 284–9. PMID 2462937.
- ^ Kirkland TN, Viriyakosol S (1998). "Structure-function analysis of soluble and membrane-bound CD14". Prog. Clin. Biol. Res. 397: 79–87. PMID 9575549.
- ^ Kelley SL, Lukk T, Nair SK, Tapping, RI (2013). "The Crystal Structure of Human Soluble CD14 Reveals a Bent Solenoid with a Hydrophobic Amino-Terminal Pocket". J. Immunol. 190 (3): 1304–1311. doi:10.4049/jimmunol.1202446. PMID 23264655.
- ^ Kitchens RL (2000). "Role of CD14 in cellular recognition of bacterial lipopolysaccharides". Chem. Immunol. Chemical Immunology and Allergy 74: 61–82. doi:10.1159/000058750. ISBN 3-8055-6917-3. PMID 10608082.
- ^ Tapping RI, Tobias PS (2000). "Soluble CD14-mediated cellular responses to lipopolysaccharide". Chem. Immunol. Chemical Immunology and Allergy 74: 108–21. doi:10.1159/000058751. ISBN 3-8055-6917-3. PMID 10608084.
- ^ Ranoa DR, Kelley SL, Tapping RI (2013). "Human LBP and CD14 independently deliver triacylated lipoproteins to TLR1 and TLR2 and enhance formation of the ternary signaling complex.". J. Biol. Chem. 74 (epub): epub. doi:10.1074/jbc.M113.453266. PMID 23430250.
- ^ a b 矢田純一 『医系免疫学』、2009年、改訂11版。ISBN 978-4-498-10602-4。
外部リンク
- CD14 Antigens - the US National Library of Medicine Medical Subject Headings (MeSH)
- [1]
- [2]
- [3]
- [4]
参考文献
- Todd RF, Petty HR (1997). "Beta 2 (CD11/CD18) integrins can serve as signaling partners for other leukocyte receptors". J. Lab. Clin. Med. 129 (5): 492–8. doi:10.1016/S0022-2143(97)90003-2. PMID 9142045.
- Kelley SL, Lukk T, Nair SK, Tapping RI (2013). "The Crystal Structure of Human Soluble CD14 Reveals a Bent Solenoid with a Hydrophobic Amino-Terminal Pocket". J.Immunol. 190 (3): 1304–1311. doi:10.4049/jimmunol.1202446. PMID 23264655.
|
この項目は、医学に関連した書きかけの項目です。この項目を加筆・訂正などしてくださる協力者を求めています（プロジェクト:医学／Portal:医学と医療）。 |
[Wiki en表示]
| CD14 molecule |
|
Rendering based on PDB 1WWL.
|
| Available structures |
| PDB |
Ortholog search: PDBe, RCSB |
| List of PDB id codes |
|
4GLP
|
|
|
| Identifiers |
| Symbol |
CD14 |
| External IDs |
OMIM: 158120 MGI: 88318 HomoloGene: 493 GeneCards: CD14 Gene |
| Gene ontology |
| Molecular function |
• lipopolysaccharide binding
• opsonin receptor activity
• protein binding
• peptidoglycan receptor activity
• lipoteichoic acid binding
|
| Cellular component |
• extracellular region
• extracellular space
• plasma membrane
• cell surface
• endosome membrane
• anchored component of membrane
• membrane raft
• extracellular exosome
|
| Biological process |
• toll-like receptor signaling pathway
• MyD88-dependent toll-like receptor signaling pathway
• MyD88-independent toll-like receptor signaling pathway
• receptor-mediated endocytosis
• phagocytosis
• apoptotic process
• inflammatory response
• cell surface receptor signaling pathway
• I-kappaB kinase/NF-kappaB signaling
• response to heat
• programmed cell death
• response to magnesium ion
• positive regulation of type I interferon production
• positive regulation of tumor necrosis factor production
• toll-like receptor 2 signaling pathway
• toll-like receptor 3 signaling pathway
• toll-like receptor 4 signaling pathway
• response to tumor necrosis factor
• TRIF-dependent toll-like receptor signaling pathway
• toll-like receptor TLR1:TLR2 signaling pathway
• toll-like receptor TLR6:TLR2 signaling pathway
• innate immune response
• response to ethanol
• positive regulation of endocytosis
• positive regulation of cytokine secretion
• response to electrical stimulus
• cellular response to lipopolysaccharide
• cellular response to lipoteichoic acid
• extrinsic apoptotic signaling pathway
• activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway
|
| Sources: Amigo / QuickGO |
|
| RNA expression pattern |
|
| More reference expression data |
| Orthologs |
| Species |
Human |
Mouse |
| Entrez |
929 |
12475 |
| Ensembl |
ENSG00000170458 |
ENSMUSG00000051439 |
| UniProt |
P08571 |
P10810 |
| RefSeq (mRNA) |
NM_000591 |
NM_009841 |
| RefSeq (protein) |
NP_000582 |
NP_033971 |
| Location (UCSC) |
Chr 5:
140.63 – 140.63 Mb |
Chr 18:
36.73 – 36.73 Mb |
| PubMed search |
[1] |
[2] |
|
|
CD14 (cluster of differentiation 14), also known as CD14, is a human gene.[1][2]
The protein encoded by this gene is a component of the innate immune system. CD14 exists in two forms, one anchored to the membrane by a glycosylphosphatidylinositol tail (mCD14), the other a soluble form (sCD14). Soluble CD14 either appears after shedding of mCD14 (48 kDa) or is directly secreted from intracellular vesicles (56 kDa).[3]
The x-ray crystal structure of human CD14 (4GLP.pdb) reveals a monomeric, bent solenoid structure containing a hydrophobic amino-terminal pocket.[4]
CD14 was the first described pattern recognition receptor.
Contents
- 1 Function
- 2 Tissue distribution
- 3 Differentiation
- 4 Interactions
- 5 References
- 6 External links
Function
CD14 acts as a co-receptor (along with the Toll-like receptor TLR 4 and MD-2) for the detection of bacterial lipopolysaccharide (LPS).[5][6] CD14 can bind LPS only in the presence of lipopolysaccharide-binding protein (LBP). Although LPS is considered its main ligand, CD14 also recognizes other pathogen-associated molecular patterns such as lipoteichoic acid.[7]
Signaling pathway of toll-like receptors. Dashed grey lines represent unknown associations
Tissue distribution
CD14 is expressed mainly by macrophages and (at 10-times lesser extent) by neutrophils. It is also expressed by dendritic cells. The soluble form of the receptor (sCD14) is secreted by the liver and monocytes and is sufficient in low concentrations to confer LPS-responsiveness to cells not expressing CD14. mCD14 and sCD14 are also present on enterocytes.[8] sCD14 is also present in human milk, where it is believed to regulate microbial growth in the infant gut.
Differentiation
CD14+ monocytes can differentiate into a host of different cells, including dendritic cells, a differentiation pathway encouraged by cytokines, including GM-CSF and IL-4.
Interactions
CD14 has been shown to interact with lipopolysaccharide-binding protein.[9][10]
References
- ^ Setoguchi M, Nasu N, Yoshida S, Higuchi Y, Akizuki S, Yamamoto S (July 1989). "Mouse and human CD14 (myeloid cell-specific leucine-rich glycoprotein) primary structure deduced from cDNA clones". Biochim. Biophys. Acta 1008 (2): 213–22. doi:10.1016/0167-4781(80)90012-3. PMID 2472171.
- ^ Simmons DL, Tan S, Tenen DG, Nicholson-Weller A, Seed B (1 January 1989). "Monocyte antigen CD14 is a phospholipid anchored membrane protein". Blood 73 (1): 284–9. PMID 2462937.
- ^ Kirkland TN, Viriyakosol S (1998). "Structure-function analysis of soluble and membrane-bound CD14". Prog. Clin. Biol. Res. 397: 79–87. PMID 9575549.
- ^ Kelley SL, Lukk T, Nair SK, Tapping, RI (2013). "The Crystal Structure of Human Soluble CD14 Reveals a Bent Solenoid with a Hydrophobic Amino-Terminal Pocket". Journal of Immunology 190 (3): 1304–1311. doi:10.4049/jimmunol.1202446. PMID 23264655.
- ^ Kitchens RL (2000). "Role of CD14 in cellular recognition of bacterial lipopolysaccharides". Chem. Immunol. Chemical Immunology and Allergy 74: 61–82. doi:10.1159/000058750. ISBN 3-8055-6917-3. PMID 10608082.
- ^ Tapping RI, Tobias PS (2000). "Soluble CD14-mediated cellular responses to lipopolysaccharide". Chem. Immunol. Chemical Immunology and Allergy 74: 108–21. doi:10.1159/000058751. ISBN 3-8055-6917-3. PMID 10608084.
- ^ Ranoa DR, Kelley SL, Tapping RI (2013). "Human LBP and CD14 independently deliver triacylated lipoproteins to TLR1 and TLR2 and enhance formation of the ternary signaling complex.". J. Biol. Chem. 74: 9729–41. doi:10.1074/jbc.M113.453266. PMID 23430250.
- ^ "CD14 Is Expressed and Released as Soluble CD14 by Human Intestinal Epithelial Cells In Vitro: Lipopolysaccharide Activation of Epithelial Cells Revisited".
- ^ Thomas, Celestine J; Kapoor Mili; Sharma Shilpi; Bausinger Huguette; Zyilan Umit; Lipsker Dan; Hanau Daniel; Surolia Avadhesha (November 2002). "Evidence of a trimolecular complex involving LPS, LPS binding protein and soluble CD14 as an effector of LPS response". FEBS Lett. (Netherlands) 531 (2): 184–8. doi:10.1016/S0014-5793(02)03499-3. ISSN 0014-5793. PMID 12417309.
- ^ Yu, B; Wright S D (1995). "LPS-dependent interaction of Mac-2-binding protein with immobilized CD14". J. Inflamm. (UNITED STATES) 45 (2): 115–25. ISSN 1078-7852. PMID 7583357.
External links
- CD14 Antigens at the US National Library of Medicine Medical Subject Headings (MeSH)
- [3]
- [4]
- [5]
- [6]
|
Cluster of differentiation by lineage
|
|
| Lymphoid |
| B cell |
- Pre-B cell: CD10/CALLA
- CD79A
- mature: CD19
- CD20
- CD21/CR2
- CD23/FcεRII
- CD127
- CD40
|
|
| T/NK |
| T cell |
- CD1
- CD4
- CD8
- CD13
- CD18
- CD26
- CD27
- CD28
|
|
| NK cell |
|
|
| All |
|
|
|
| All |
|
|
|
| Myeloid |
CFU-GM/
Myelomonocyte |
- CD11c
- CD14
- CD15
- CD31
- CD64
- CD68
|
|
| MEP |
|
|
| All (pan-myeloid) |
|
|
|
| Stem cell |
|
|
|
Index of cells from bone marrow
|
|
| Description |
- Immune system
- Cells
- Physiology
- coagulation
- proteins
- granule contents
- colony-stimulating
- heme and porphyrin
|
|
| Disease |
- Red blood cell
- Monocyte and granulocyte
- Neoplasms and cancer
- Histiocytosis
- Symptoms and signs
- Blood tests
|
|
| Treatment |
- Transfusion
- Drugs
- thrombosis
- bleeding
- other
|
|
Index of the immune system
|
|
| Description |
- Physiology
- cells
- autoantigens
- autoantibodies
- complement
- surface antigens
- IG receptors
|
|
| Disease |
- Allergies
- Immunodeficiency
- Immunoproliferative immunoglobulin disorders
- Hypersensitivity and autoimmune disorders
- Neoplasms and cancer
|
|
| Treatment |
- Procedures
- Drugs
- antihistamines
- immunostimulants
- immunosuppressants
- monoclonal antibodies
|
|
|
|
Signaling pathway: TLR signaling pathway
|
|
| Receptor |
|
|
| Other external |
|
|
| Internal |
- adaptor: MYD88
- TRIF
- TIRAP
- TRAF6
- TOLLIP
|
|
|
|
|
|
|
|
|
|
|
|
|
Index of signal transduction
|
|
| Description |
- Intercellular
- neuropeptides
- growth factors
- cytokines
- hormones
- Cell surface receptors
- ligand-gated
- enzyme-linked
- G protein-coupled
- immunoglobulin superfamily
- integrins
- neuropeptide
- growth factor
- cytokine
- Intracellular
- adaptor proteins
- GTP-binding
- MAP kinase
- Calcium signaling
- Lipid signaling
- Pathways
- hedgehog
- Wnt
- TGF beta
- MAPK ERK
- notch
- JAK-STAT
- apoptosis
- hippo
- TLR
|
|
|
UpToDate Contents
全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.
English Journal
- Interferon stimulated genes, CXCR4 and immune cell responses in peripheral blood mononuclear cells infected with bovine viral diarrhea virus.
- Weiner CM, Smirnova NP, Webb BT, Van Campen H, Hansen TR.SourceAnimal Reproduction and Biotechnology Laboratory, Department of Biomedical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA; Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
- Research in veterinary science.Res Vet Sci.2012 Oct;93(2):1081-8. Epub 2012 Feb 18.
- Non-cytopathic bovine viral diarrhea virus (ncpBVDV) induces immune responses mediated by chemokines and interferon (IFN) stimulated genes (ISGs). Cultured bovine peripheral blood mononuclear cells (PBMC) from ncpBVDV-naïve cattle were used herein to demonstrate that BVDV infection modulates chemok
- PMID 22349591
- Pravastatin reverses the membrane cholesterol reorganization induced by myocardial infarction within lipid rafts in CD14(+)/CD16(-) circulating monocytes.
- Salvary T, Gambert-Nicot S, Brindisi MC, Meneveau N, Schiele F, Séronde MF, Lorgis L, Zeller M, Cottin Y, Kantelip JP, Gambert P, Davani S.SourceIFR100 SANTE-STIC-INSERM, Université de Bourgogne, Dijon, France.
- Biochimica et biophysica acta.Biochim Biophys Acta.2012 Sep;1821(9):1287-94. Epub 2012 Mar 15.
- Large numbers of monocytes are recruited in the infarcted myocardium. Their cell membranes contain cholesterol-rich microdomains called lipids rafts, which participate in numerous signaling cascades. In addition to its cholesterol-lowering effect, pravastatin has several pleiotropic effects and is w
- PMID 22425357
- The three human monocyte subsets: implications for health and disease.
- Wong KL, Yeap WH, Tai JJ, Ong SM, Dang TM, Wong SC.SourceSingapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, #04/04, Immunos, Biopolis, Singapore, 138648, Singapore.
- Immunologic research.Immunol Res.2012 Sep;53(1-3):41-57.
- Human blood monocytes are heterogeneous and conventionally subdivided into two subsets based on CD16 expression. Recently, the official nomenclature subdivides monocytes into three subsets, the additional subset arising from the segregation of the CD16+ monocytes into two based on relative expressio
- PMID 22430559
Japanese Journal
- 敗血症診断マーカーとしてのプレセプシン(可溶性CD14サブタイプ)の有用性
- 遠藤 重厚,高橋 学,小豆島 立頼,松本 尚也,小鹿 雅博,鈴木 泰,井上 義博
- 岩手医学雑誌 64(1), 1-14, 2012-04-01
- NAID 110009421582
- Chaetoglobosin Fex from the Marine-Derived Endophytic Fungus Inhibits Induction of Inflammatory Mediators via Toll-Like Receptor 4 Signaling in Macrophages
- DOU Huan,SONG Yuxian,LIU Xianqin [他]
- Biological & pharmaceutical bulletin 34(12), 1864-1873, 2011-12
- NAID 40019073547
- Aberrant splicing of the hRasGRP4 transcript and decreased levels of this signaling protein in the peripheral blood mononuclear cells in a subset of patients with rheumatoid arthritis
- Hashimoto Toko,Yasuda Shinsuke,Koide Hideyuki,Kataoka Hiroshi,Horita Tetsuya,Atsumi Tatsuya,Koike Takao
- Arthritis Research & Therapy 13(5), R154, 2011-09-20
- … Results: Circulating CD14+ cells in normal individuals were found to express hRasGRP4. …
- NAID 120003945421
Related Links
- CD14抗原は、分子量53-55kDaのグリコシル-ホスファチジルイノシトール（GPI）結合型 単鎖膜糖タンパクです。リポ多糖類（LPS）とLPS ... CD14抗原は骨髄単球系細胞にみ られ、単球やマクロファージに強く発現し、好中球に弱く発現します。またB細胞にも弱く ...
- CD45-FITC / CD14-PE 【リンパ球ゲートチェック用】 ... リンパ球領域（CD45+CD14－） から赤血球（CD45－CD14－）および単球（CD45+CD14+）を除外するためのゲー ティングコントロールです。
Related Pictures
★リンクテーブル★
[★]
- 英
- lipopolysaccharide, LPS
- 同
- リポ多糖類、リポポリサッカライド
- 主にマクロファージを刺激して多彩な生理作用を表す
LPSの生物活性 (SMB.115-117)
- 2. ポリクローナルB細胞活性化：B細胞を刺激し、抗原非特異的に抗体産生細胞へと分化誘導。IgMクラスの抗体を産生させる。
- 3. マクロファージの活性化：サイトカイン(IL-1、TNF-α、IFN、コロニー刺激因子(CSF)など)、フリーラジカルを放出させる。
- 4. 補体の古典的経路、別経路を活性化
- 5. アラキドン酸代謝経路の刺激：ロイコトリエン、プロスタグランジンの産生亢進
- 6. 白血球との結合：生体ではLPS投与後1時間目に顆粒球減少(白血球凝集や末梢血管への貯留による)。2-4時間後、急激に白血球増加(骨髄の顆粒球の放出や顆粒球産
生の増加による)
- 7. 血小板の活性化と破壊：セロトニン、核酸、血小板因子3などを放出。LPSにより破壊されやすい
- 8. NK細胞やNKT細胞によるIFN-γの産生亢進
リポ多糖の受容体
- →リポ多糖受容体=CD14
リポ多糖のクリアランス(SMB.117)
- 血流に入ったLPSは、LPS結合タンパク質(LBP)や遊離CD14と結合し、ついで血清タンパク質(特に高比重リポタンパク質(HDL)と結合し、速やかに主に肝臓に取り込まれる。肝臓、脾臓などのマクロファージ系の貪食細胞がLPSを捕獲し、比較的長い時間かかって分解するらしい。
リポ多糖の臨床的意義 (SMB.117-118)
エンドトキシンショック
抗生物質誘発内毒素遊離
- 内毒素は菌が増殖するときに、外膜より遊離。
- ある種の抗生物質は菌を殺す際、大量の内毒素の遊離を招く
検査
[★]
- 英
- cluster of differentiation, CD
- Bリンパ球 CD10,CD19,CD20
- Tリンパ球 CD2,CD3,CD5,CD7
- 幹細胞 CD34
- 顆粒球 CD13,CD33
- 単球 CD14：LPSをリガンドとし、Toll-like receptorと共役して細胞内シグナルを伝達する分子。
- 巨核球 CD41(GpIIb),CD42(GpIb)
- NK細胞：CD16(IgGのFc部に対する受容体)、CD56(NCAM-I)
[★]
- 英
- presepsin
- 関
- 炎症マーカー、可溶性CD14 subtype、CD14
参考
- http://knight1112jp.at.webry.info/201308/article_6.html
[★]
CD14。リポ多糖受容体
[★]
アンジオテンシン変換酵素
[★]
- 同
- leucine-6, CD1A through E
種類
発現組織
- 胸腺皮質、ランゲルハンス細胞、樹状細胞、B細胞(CD1c)、腸上皮、平滑筋、血管上皮(CD1d)
分子量
機能
- MHC class I-like molecule, associated with β2-microgloulin. Has specialized role in presentation of lipid antigens
[★]
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