BPIF binds bacteria

Stable Identifier
R-HSA-6809521
Type
Reaction [binding]
Species
Homo sapiens
Compartment
ReviewStatus
5/5
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BPI fold-containing (BPIF) proteins (known as PLUNC (palate, lung and nasal epithelium clone) proteins) are expressed largely in the respiratory tract of air-breathing vertebrates (Bingle CD et al. 2011). Due to both the presence at host-pathogen interface and sequence/structural similarities to members of a lipid-transfer protein family such as bactericidal/permeability-increasing (BPI) and lipopolysaccharide-binding (LBP) proteins, the BPIF family of proteins are predicted to have host-protective functions (Bingle CD & Craven CJ 2002, 2003; Beamer et al. 1997; Bingle CD et al. 2004; 2011). Although the BPIF proteins are thought to have the ability to bind to and transfer lipid molecules, their biological antimicrobial properties have yet to be elucidated (Bingle CD & Craven CJ 2003; ).

BPIFs are subdivided into two groups, the long (BPIFB or LPLUNC) and short (BPIFA or SPLUNC) proteins. The BPIFB (LPLUNC) proteins have sequence and structure homology to both the LPS-binding N-terminus and the C-terminus of BPI, which is responsible for its opsonization activity, and BPIFA (SPLUNC) have homology to only the N-terminal half of BPI (....). It is proposed that the BPIF proteins may function in an antimicrobial manner, however, showed a high degree of conservation of genomic organization and of exon sizes. all show the same conservation of two cysteine residues which form a critical disulphide bond (Beamer et al. 1997) The function of the BPIF family of proteins has yet to be elucidated, but due to their predicted structure and their similarity in gene location to known LPS binding proteins, BPI and LBP, it is proposed that they function in an antimicrobial manner may function in the innate immune system, against gram negative bacterial LPS, either by acting directly against bacteria in a bactericidal manner, initiating an immune response or as an anti-toxin, by reducing the inflammatory response.All members of this family appear to have the ability to bind to and transfer lipid molecules (Bingle and Craven, 2003). BPIFA1 (SPLUNC1) is secreted in the epithelium of the upper airways, where it coats the surface of the epithelium and cilia, but significantly greater expression is seen in the submucosal cells and ducts of glands associated with the upper airways (Campos MA et al. 2004; Di YP et al. 2003; Bingle L et al. 2005; Bingle L & Bingle CD 2011). BPIFA1 is considered to contribute to mucosa immunity protecting the upper airway from infections. The antibacterial properties BPIFA1 have been demonstrated with regard to Staphylococcus aureus, Streptococcus, Pseudomonas, Mycoplasma pneumonia and Klebsiella pneumonia (Di YP 2011; Gally F et al. 2011; Tsou YA et al. 201; Liu Y et al. 2013). It is also considered to have antibiofilm functionality through its ability to modulate surface tension of airway fluids (Gakhar L et al. 2010; Bartlett JA et al. 2011; Liu Y et al. 2013). In addition, BPIFA1 negatively regulates epithelial sodium channel (ENaC) function, affecting the height of the airway surface liquid, which is essential for adequate mucociliary clearance (Garcia-Caballero A et al. 2009; Hobbs CA et al. 2013; Tarran R & Redinbo MR 2014). Furthermore, BPIFA1 also shows immunomodulatory properties in different mouse models of acute airway inflammations (). The high level of BPIFA1 present in the airways under basal conditions fluctuating rapidly in response to environmental stress and upon airway inflammation. The fluctuations in the BPIFA1 levels are thought to help the local milieu in optimizing protective functions in the airways (Bingle L et al. 2007; Britto CJ and Cohn L 2015). SPLUNC2 is expressed in serous cells of the major salivary glands and in minor mucosal glands mainly secreted from the upper airway.

Literature References
PubMed ID Title Journal Year
11971875 PLUNC: a novel family of candidate host defence proteins expressed in the upper airways and nasopharynx

Craven, CJ, Bingle, CD

Hum. Mol. Genet. 2002
14739326 Phylogenetic and evolutionary analysis of the PLUNC gene family

Havard, S, Craven, CJ, Gillingham, P, Bingle, CD, LeClair, EE, Bingle, L

Protein Sci. 2004
21787330 Distant cousins: genomic and sequence diversity within the BPI fold-containing (BPIF)/PLUNC protein family

Craven, CJ, Bingle, CD, Bingle, L

Biochem. Soc. Trans. 2011
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