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.
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.
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. What makes SLPI such a topic of interest is that it exhibits anti-HIV properties in physiological conditions, rather than artificial ones.
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.
SLPI has been shown to interact with PLSCR1 and PLSCR4 on the plasma membrane of T-cells, specifically in the proximity of CD4. 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. This interaction with A2t has also been shown to block HPV uptake and infection of epithelial cells.
^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. PMID9815215.
^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. PMID8373998.
^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. PMID23996702.
^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. PMID10869562.
Sallenave JM, Ryle AP (Jan 1991). "Purification and characterization of elastase-specific inhibitor. Sequence homology with mucus proteinase inhibitor". Biological Chemistry Hoppe-Seyler. 372 (1): 13–21. doi:10.1515/bchm3.1991.372.1.13. PMID2039600.
Eisenberg SP, Hale KK, Heimdal P, Thompson RC (May 1990). "Location of the protease-inhibitory region of secretory leukocyte protease inhibitor". The Journal of Biological Chemistry. 265 (14): 7976–81. PMID2110563.
Seemüller U, Arnhold M, Fritz H, Wiedenmann K, Machleidt W, Heinzel R, Appelhans H, Gassen HG, Lottspeich F (Apr 1986). "The acid-stable proteinase inhibitor of human mucous secretions (HUSI-I, antileukoprotease). Complete amino acid sequence as revealed by protein and cDNA sequencing and structural homology to whey proteins and Red Sea turtle proteinase inhibitor". FEBS Letters. 199 (1): 43–8. doi:10.1016/0014-5793(86)81220-0. PMID3485543.
Heinzel R, Appelhans H, Gassen G, Seemüller U, Machleidt W, Fritz H, Steffens G (Oct 1986). "Molecular cloning and expression of cDNA for human antileukoprotease from cervix uterus". European Journal of Biochemistry / FEBS. 160 (1): 61–7. doi:10.1111/j.1432-1033.1986.tb09940.x. PMID3533531.
Westin U, Fryksmark U, Polling A, Ohlsson K (Mar 1994). "Localisation of secretory leucocyte proteinase inhibitor mRNA in nasal mucosa". Acta Oto-Laryngologica. 114 (2): 199–202. doi:10.3109/00016489409126042. PMID7515550.
Ohlsson K, Bjartell A, Lilja H (1995). "Secretory leucocyte protease inhibitor in the male genital tract: PSA-induced proteolytic processing in human semen and tissue localization". Journal of Andrology. 16 (1): 64–74. PMID7539415.
Kikuchi T, Abe T, Hoshi S, Matsubara N, Tominaga Y, Satoh K, Nukiwa T (Dec 1998). "Structure of the murine secretory leukoprotease inhibitor (Slpi) gene and chromosomal localization of the human and murine SLPI genes". American Journal of Respiratory Cell and Molecular Biology. 19 (6): 875–80. doi:10.1165/ajrcmb.19.6.3314. PMID9843921.
Westin U, Polling A, Ljungkrantz I, Ohlsson K (Apr 1999). "Identification of SLPI (secretory leukocyte protease inhibitor) in human mast cells using immunohistochemistry and in situ hybridisation". Biological Chemistry. 380 (4): 489–93. doi:10.1515/BC.1999.063. PMID10355635.
Si-Tahar M, Merlin D, Sitaraman S, Madara JL (Jun 2000). "Constitutive and regulated secretion of secretory leukocyte proteinase inhibitor by human intestinal epithelial cells". Gastroenterology. 118 (6): 1061–71. doi:10.1016/S0016-5085(00)70359-3. PMID10833481.
Victor E. Reviglio, Andres Grenat, Federico Pegoraro, Ruben H. Sambuelli, Tayyib Rana, and Irene C. Kuo. Secretory Leukoprotease Inhibitor: A Native Antimicrobial Protein in the Innate Immune Response in a Rat Model of S. aureus Keratitis. Journal of OphthalmologyVolume 2009 (2009), Article ID 259393, 5 pages doi:10.1155/2009/259393