# BPIFA2

## Overview
BPIFA2, or BPI fold containing family A member 2, is a gene that encodes a salivary surfactant protein known as Parotid Secretory Protein (PSP) or SPLUNC2. This protein is primarily expressed in the salivary glands and plays a crucial role in the innate immune system by modulating the physical properties of saliva and binding to lipopolysaccharides (LPS) on bacterial surfaces. As a member of the BPI fold-containing family, BPIFA2 is involved in host defense mechanisms, exhibiting antimicrobial activity and contributing to the protection against bacterial infections and endotoxemia. The protein's interactions with various microbial components underscore its significance in immune modulation and its potential implications in clinical conditions such as Sjögren's syndrome and radiation-induced salivary gland hypofunction (Nandula2020The; Abdolhosseini2011Human; Bingle2011Distribution).

## Function
BPIFA2, also known as Parotid Secretory Protein (PSP), is a salivary surfactant protein primarily expressed in the salivary glands. It plays a significant role in modulating the physical properties of saliva, contributing to its surfactant properties, which are crucial for the 'wetting' of mucosal surfaces (Nandula2020The). BPIFA2 binds to lipopolysaccharides (LPS) on bacterial surfaces, which is a key aspect of its function in innate immunity, helping to inhibit bacterial growth and potentially modulating inflammatory responses (Nandula2020The; Abdolhosseini2011Human). 

In healthy human cells, BPIFA2 is secreted into saliva from the major and minor salivary glands, where it is involved in host defense mechanisms, including antimicrobial activity and lipid binding (Nandula2020The; Bingle2011Distribution). The protein's ability to bind LPS suggests a role in protecting against endotoxemia from ingested LPS, which may influence metabolic processes related to insulin and fatty acid metabolism (Nandula2020The). BPIFA2's expression is notably high in species that practice coprophagy, indicating a potential role in nutrient extraction or LPS protection (Nandula2020The).

## Clinical Significance
BPIFA2, also known as Parotid Secretory Protein (PSP), has been implicated in several clinical conditions due to its role in salivary function and immune response. Alterations in BPIFA2 expression have been observed in patients undergoing head and neck cancer radiotherapy, where decreased levels of glycosylated BPIFA2 were noted. This reduction is associated with radiation-induced salivary gland hypofunction, which can lead to decreased salivary flow and changes in saliva composition, potentially affecting the quality of life and increasing the risk of oral conditions like candidiasis (GonzálezArriagada2015Salivary).

BPIFA2 has also been linked to autoimmune conditions such as Sjögren's syndrome. In mouse models, the depletion of BPIFA2 has been associated with Sjögren's syndrome-like symptoms and the presence of autoantibodies in patients, suggesting its clinical significance in such autoimmune disorders (Nandula2020The). Additionally, BPIFA2 expression is altered in the context of periodontitis and in HIV patients co-infected with CMV or mycobacteria, indicating its potential involvement in these conditions (Bingle2011Distribution).

The protein's role in binding lipopolysaccharides (LPS) and its impact on systemic metabolic processes further highlight its importance in maintaining normal physiological functions and preventing conditions like mild metabolic endotoxemia (Nandula2020The).

## Interactions
BPIFA2, also known as Parotid Secretory Protein (PSP) or SPLUNC2, is a salivary surfactant protein involved in various interactions with other proteins and molecules. It is known for its ability to bind lipopolysaccharides (LPS), which are components of the outer membrane of Gram-negative bacteria, suggesting a role in modulating bacterial interactions and immune responses (Prokopovic2014Isolation; Nandula2020The). BPIFA2 also binds to Candida albicans, facilitating its adherence to silicone surfaces, which indicates its involvement in microbial colonization processes (Holmes2014Adherence).

The protein exhibits antimicrobial activity, particularly against Pseudomonas aeruginosa, by inhibiting its growth and demonstrating bactericidal properties (Prokopovic2014Isolation). BPIFA2 is part of a cluster of genes, including CXCL6, SAA2, and SAA4, that are upregulated in response to LPS exposure, suggesting its role in systemic septic responses and damage-limiting biological processes (Sallustio2019Renal). In renal progenitor cells, BPIFA2 is secreted to counteract LPS-induced endothelial-to-mesenchymal transition, highlighting its protective role in sepsis-induced kidney damage (Sallustio2019Renal). These interactions underscore BPIFA2's significance in host defense and immune modulation.


## References


[1. (Sallustio2019Renal) Fabio Sallustio, Alessandra Stasi, Claudia Curci, Chiara Divella, Angela Picerno, Rossana Franzin, Giuseppe De Palma, Monica Rutigliano, Giuseppe Lucarelli, Michele Battaglia, Francesco Staffieri, Antonio Crovace, Giovanni Battista Pertosa, Giuseppe Castellano, Anna Gallone, and Loreto Gesualdo. Renal progenitor cells revert lps‐induced endothelial‐to‐mesenchymal transition by secreting cxcl6, saa4, and bpifa2 antiseptic peptides. The FASEB Journal, 33(10):10753–10766, July 2019. URL: http://dx.doi.org/10.1096/fj.201900351r, doi:10.1096/fj.201900351r. This article has 34 citations.](https://doi.org/10.1096/fj.201900351r)

[2. (Abdolhosseini2011Human) Mahsa Abdolhosseini, Julie B. Sotsky, Anuradha P. Shelar, Paul B. M. Joyce, and Sven-Ulrik Gorr. Human parotid secretory protein is a lipopolysaccharide-binding protein: identification of an anti-inflammatory peptide domain. Molecular and Cellular Biochemistry, 359(1–2):1–8, July 2011. URL: http://dx.doi.org/10.1007/s11010-011-0991-2, doi:10.1007/s11010-011-0991-2. This article has 33 citations and is from a peer-reviewed journal.](https://doi.org/10.1007/s11010-011-0991-2)

[3. (Holmes2014Adherence) A.R. Holmes, E. Rodrigues, P. van der Wielen, K.M. Lyons, B.J. Haigh, T.T. Wheeler, P.J.D. Dawes, and R.D. Cannon. Adherence of candida albicans to silicone is promoted by the human salivary protein <scp>splunc</scp>2/<scp>psp</scp>/<scp>bpifa</scp>2. Molecular Oral Microbiology, 29(2):90–98, February 2014. URL: http://dx.doi.org/10.1111/omi.12048, doi:10.1111/omi.12048. This article has 13 citations and is from a peer-reviewed journal.](https://doi.org/10.1111/omi.12048)

[4. (Nandula2020The) Seshagiri Rao Nandula, Ian Huxford, Thomas T. Wheeler, Conrado Aparicio, and Sven‐Ulrik Gorr. The parotid secretory protein bpifa2 is a salivary surfactant that affects lipopolysaccharide action. Experimental Physiology, 105(8):1280–1292, June 2020. URL: http://dx.doi.org/10.1113/EP088567, doi:10.1113/ep088567. This article has 9 citations and is from a peer-reviewed journal.](https://doi.org/10.1113/EP088567)

[5. (Prokopovic2014Isolation) Vladimir Prokopovic, Milica Popovic, Uros Andjelkovic, Aleksandra Marsavelski, Brankica Raskovic, Marija Gavrovic-Jankulovic, and Natalija Polovic. Isolation, biochemical characterization and anti-bacterial activity of bpifa2 protein. Archives of Oral Biology, 59(3):302–309, March 2014. URL: http://dx.doi.org/10.1016/j.archoralbio.2013.12.005, doi:10.1016/j.archoralbio.2013.12.005. This article has 19 citations and is from a peer-reviewed journal.](https://doi.org/10.1016/j.archoralbio.2013.12.005)

[6. (Bingle2011Distribution) Lynne Bingle and Colin D. Bingle. Distribution of human plunc/bpi fold-containing (bpif) proteins. Biochemical Society Transactions, 39(4):1023–1027, July 2011. URL: http://dx.doi.org/10.1042/bst0391023, doi:10.1042/bst0391023. This article has 52 citations and is from a peer-reviewed journal.](https://doi.org/10.1042/bst0391023)

[7. (GonzálezArriagada2015Salivary) Wilfredo Alejandro González-Arriagada, Lara Maria Alencar Ramos, Andreia Aparecida Silva, Pablo Agustin Vargas, Ricardo Della Coletta, Lynne Bingle, and Marcio Ajudarte Lopes. Salivary bpifa1 (splunc1) and bpifa2 (splunc2 a) are modified by head and neck cancer radiotherapy. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 119(1):48–58, January 2015. URL: http://dx.doi.org/10.1016/j.oooo.2014.09.026, doi:10.1016/j.oooo.2014.09.026. This article has 9 citations and is from a peer-reviewed journal.](https://doi.org/10.1016/j.oooo.2014.09.026)