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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/04/06 16:33:36」(JST)

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Antileukoproteinase, also known as secretory leukocyte protease inhibitor (SLPI), is an enzyme that in humans is encoded by the SLPI gene.^[1]^[2]^[3] SLPI is a highly cationic single-chain protein with eight intramolecular disulfide bonds. It is found in large quantities in bronchial, cervical, and nasal mucosa, saliva, and seminal fluids. SLPI inhibits human leukocyte elastase, human cathepsin G, human trypsin, neutrophil elastase, and mast cell chymase. X-ray crystallography has shown that SLPI has two homologous domains of 53 and 54 amino acids, one of which exhibits anti-protease activity (C-terminal domain). The other domain (N-terminal domain) is not known to have any function.

Function

This gene encodes a secreted inhibitor which protects epithelial tissues from serine proteases. It is found in various secretions including seminal plasma, cervical mucus, and bronchial secretions, and has affinity for trypsin, leukocyte elastase, and cathepsin G. Its inhibitory effect contributes to the immune response by protecting epithelial surfaces from attack by endogenous proteolytic enzymes; the protein is also thought to have broad-spectrum anti-biotic activity.^[3]

Clinical significance

The gene for SLPI is expressed by cells at many mucosal surfaces located in the tissues of the lungs, cervix, seminal vesicles, and parotid ducts. SLPI is also one of the dominantly present proteins in nasal epithelial lining fluid and other nasal secretions. Many diseases, such as emphysema, cystic fibrosis, and idiopathic pulmonary fibrosis, are characterized by increased levels of neutrophil elastase. SLPI is one of the major defenses against the destruction of pulmonary tissues and epithelial tissues by neutrophil elastase. SLPI is considered to be the predominant elastase inhibitor in secretions, while α1-antitrypsin is the predominant elastase inhibitor in tissues. Several diseases, including those listed, are actually the result of SLPI and α1-antitrypsin defenses being overwhelmed by neutrophil elastase. It has been suggested that recombinant human SLPI be administered to treat symptoms of cystic fibrosis, genetic emphysema, and asthma. In addition, SLPI has occasionally been monitored in an effort to coordinate its levels with different pathological conditions. Increased levels of SLPI in nasal secretions and bronchoalveolar fluids may be denotive of inflammatory lung conditions or allergic reactions, and increased levels of SLPI in plasma may be indicative of pneumonia.^[4]

Increased levels of SLPI in saliva and plasma may also be an indicator of HIV infection. This is evident due to the virtual nonexistence of HIV transmission through oral-to-oral contact. This antiviral activity is due to the interference of SLPI in events that are mediated by protease, such as entry into the host cell and replication of viral genetic material. Studies have shown that decreasing levels of SLPI in saliva also decreases its anti-HIV activity.^[4]^[5]^[6]^[7] What makes SLPI such a topic of interest is that it exhibits anti-HIV properties in physiological conditions, rather than artificial ones.^[4]

Furthermore, it has been shown that there is an inverse correlation between the levels of SLPI and high-risk Human Papillomavirus (HPV) infection, demonstrating that high levels of SLPI confer protection against HPV infection.^[8]^[9]^[10]

Interactions

SLPI has been shown to interact with PLSCR1 and PLSCR4 on the plasma membrane of T-cells, specifically in the proximity of CD4.^[11]^[12] This interaction is hypothesized to be one of the ways SLPI inhibits HIV infection.

Additionally, it has been shown that SLPI is able to bind the Annexin A2/S100A10 heterotetramer (A2t), a co-factor HIV infection, on the surface of macrophages.^[13] This interaction with A2t has also been shown to block HPV uptake and infection of epithelial cells.^[14]

References

^ Stetler G, Brewer MT, Thompson RC (Oct 1986). "Isolation and sequence of a human gene encoding a potent inhibitor of leukocyte proteases". Nucleic Acids Research 14 (20): 7883–96. doi:10.1093/nar/14.20.7883. PMC 311822. PMID 3640338.
^ Clauss A, Lilja H, Lundwall A (Nov 2002). "A locus on human chromosome 20 contains several genes expressing protease inhibitor domains with homology to whey acidic protein". The Biochemical Journal 368 (Pt 1): 233–42. doi:10.1042/BJ20020869. PMC 1222987. PMID 12206714.
^ ^a ^b "Entrez Gene: SLPI secretory leukocyte peptidase inhibitor".
^ ^a ^b ^c McNeely TB, Dealy M, Dripps DJ, Orenstein JM, Eisenberg SP, Wahl SM (Jul 1995). "Secretory leukocyte protease inhibitor: a human saliva protein exhibiting anti-human immunodeficiency virus 1 activity in vitro". The Journal of Clinical Investigation 96 (1): 456–64. doi:10.1172/JCI118056. PMC 185219. PMID 7615818.
^ Nagashunmugam T, Malamud D, Davis C, Abrams WR, Friedman HM (Dec 1998). "Human submandibular saliva inhibits human immunodeficiency virus type 1 infection by displacing envelope glycoprotein gp120 from the virus". The Journal of Infectious Diseases 178 (6): 1635–41. doi:10.1086/314511. PMID 9815215.
^ Shugars DC, Wahl SM (Jul 1998). "The role of the oral environment in HIV-1 transmission". Journal of the American Dental Association 129 (7): 851–8. doi:10.14219/jada.archive.1998.0349. PMID 9685760.
^ Malamud D, Friedman HM (1993-01-01). "HIV in the oral cavity: virus, viral inhibitory activity, and antiviral antibodies: a review". Critical Reviews in Oral Biology and Medicine 4 (3-4): 461–6. PMID 8373998.
^ Hoffmann M, Quabius ES, Tribius S, Hebebrand L, Görögh T, Halec G, Kahn T, Hedderich J, Röcken C, Haag J, Waterboer T, Schmitt M, Giuliano AR, Kast WM (May 2013). "Human papillomavirus infection in head and neck cancer: the role of the secretory leukocyte protease inhibitor". Oncology Reports 29 (5): 1962–8. doi:10.3892/or.2013.2327. PMC 3658815. PMID 23467841.
^ Pierce Campbell CM, Guan W, Sprung R, Koomen JM, O'Keefe MT, Ingles DJ, Abrahamsen M, Giuliano AR (Dec 2013). "Quantification of secretory leukocyte protease inhibitor (SLPI) in oral gargle specimens collected using mouthwash". Journal of Immunological Methods. 400-401: 117–21. doi:10.1016/j.jim.2013.10.005. PMC 3990009. PMID 24140751.
^ Quabius ES, Möller P, Haag J, Pfannenschmidt S, Hedderich J, Görögh T, Röcken C, Hoffmann M (Mar 2014). "The role of the antileukoprotease SLPI in smoking-induced human papillomavirus-independent head and neck squamous cell carcinomas". International Journal of Cancer. Journal International du Cancer 134 (6): 1323–34. doi:10.1002/ijc.28462. PMID 23996702.
^ Tseng CC, Tseng CP (Jun 2000). "Identification of a novel secretory leukocyte protease inhibitor-binding protein involved in membrane phospholipid movement". FEBS Letters 475 (3): 232–6. doi:10.1016/s0014-5793(00)01700-2. PMID 10869562.
^ Py B, Basmaciogullari S, Bouchet J, Zarka M, Moura IC, Benhamou M, Monteiro RC, Hocini H, Madrid R, Benichou S (2009-01-01). "The phospholipid scramblases 1 and 4 are cellular receptors for the secretory leukocyte protease inhibitor and interact with CD4 at the plasma membrane". PLOS ONE 4 (3): e5006. doi:10.1371/journal.pone.0005006. PMC 2659420. PMID 19333378.
^ Ma G, Greenwell-Wild T, Lei K, Jin W, Swisher J, Hardegen N, Wild CT, Wahl SM (Nov 2004). "Secretory leukocyte protease inhibitor binds to annexin II, a cofactor for macrophage HIV-1 infection". The Journal of Experimental Medicine 200 (10): 1337–46. doi:10.1084/jem.20041115. PMC 2211913. PMID 15545357.
^ Woodham AW, Da Silva DM, Skeate JG, Raff AB, Ambroso MR, Brand HE, Isas JM, Langen R, Kast WM (2012-01-01). "The S100A10 subunit of the annexin A2 heterotetramer facilitates L2-mediated human papillomavirus infection". PLOS ONE 7 (8): e43519. doi:10.1371/journal.pone.0043519. PMC 3425544. PMID 22927980.

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1. 資源の限られた地域における授乳によるHIV感染の予防 prevention of hiv transmission during breastfeeding in resource limited settings

English Journal

SLPI and trappin-2 as therapeutic agents to target airway serine proteases in inflammatory lung diseases: current and future directions.

Zani ML, Tanga A, Saidi A, Serrano H, Dallet-Choisy S, Baranger K, Moreau T.SourceINSERM U618, Proteases et Vectorisation Pulmonaires, Faculte de Medecine, 10 Bd Tonnelle, 37032 Tours Cedex, France.
Biochemical Society transactions.Biochem Soc Trans.2011 Oct 1;39(5):1441-6.
It is now clear that NSPs (neutrophil serine proteases), including elastase, Pr3 (proteinase 3) and CatG (cathepsin G) are major pathogenic determinants in chronic inflammatory disorders of the lungs. Two unglycosylated natural protease inhibitors, SLPI (secretory leucocyte protease inhibitor) and e
PMID 21936830

Japanese Journal

妊婦血中および頚管腟分泌液におけるHIV-1 ウイルス量とSecretory Leukocyte Protease Inhibitor 値に関する検討─ HIV 母子感染対策の観点より─

大島教子,稲葉憲之,林田志峯,根岸正実,庄田亜紀子,岡崎隆行,多田和美,西川正能,田所望,北澤正文,深澤一雄,渡辺博
Dokkyo journal of medical sciences 38(1), 95-102, 2011-03-25
… protease inhibitor (SLPI) とHIV-VL の関連を調査,経腟分娩時に軟産道となる子宮頚管局所のHIV-1 感染防御機序を検討した.方法は39名のHIV-1 感染妊婦( 米国人) のCVF 中および血中のSLPI 値とHIV-VL を測定,両者の関連を調べた.その結果,一部の症例ではCVF 中HIV-VL が血中HIV-VL より高値を示し,母体血中HIV-VL のみで分娩方法を判断する事に検討を要すると考えられた.一方,CVF 中SLPI 値は妊婦におい …
NAID 110008439919

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★リンクテーブル★

リンク元	「secretory leukocyte peptidase inhibitor」「分泌型白血球ペプチダーゼ阻害物質」
関連記事	「SL」

「secretory leukocyte peptidase inhibitor」

Secretory leukocyte peptidase inhibitor
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	2Z7F, 4DOQ
Identifiers
Symbols	SLPI ; ALK1; ALP; BLPI; HUSI; HUSI-I; MPI; WAP4; WFDC4
External IDs	OMIM: 107285 MGI: 109297 HomoloGene: 2305 GeneCards: SLPI Gene
Gene ontology
Molecular function	• endopeptidase inhibitor activity; • serine-type endopeptidase inhibitor activity; • protein binding; • enzyme binding;
Cellular component	• extracellular space; • extracellular matrix; • extracellular exosome;
Biological process	• negative regulation of endopeptidase activity; • antibacterial humoral response; • negative regulation of protein binding; • negative regulation of viral genome replication;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	v; t; e;