Functional roles of SPLUNC1 in the innate immune response against Gram-negative bacteria

Abstract

PLUNC (palate, lung and nasal epithelium clone)-associated gene originally referred to one gene, but now has been extended to represent a gene family that consists of a number of genes with peptide sequence homologies and predicted structural similarities. PLUNC-like proteins display sequence homology with BPI (bactericidal/permeability-increasing protein), a 456-residue cationic protein produced by precursors of polymorphonuclear leucocytes that have been shown to possess both bactericidal and LPS (lipopolysaccharide)-binding activities. The human PLUNC is also known as LUNX (lung-specific X protein), NASG (nasopharyngeal carcinoma-related protein) and SPURT (secretory protein in upper respiratory tract). The gene originally named PLUNC is now recognized as SPLUNC1. Its gene product SPLUNC1 is a secretory protein that is abundantly expressed in cells of the surface epithelium in the upper respiratory tracts and secretory glands in lung, and in the head and the neck region. The functional role of SPLUNC1 in innate immunity has been suggested but not clearly defined. The present review describes recent findings that support antimicrobial and anti-inflammatory functions of SPLUNC1 in Gram-negative bacteria-induced respiratory infection.

Figure 1. The relative abundance of SPLUNC1 and LPLUNC1 gene expression in various human tissues

Taqman based real time RT-PCR analysis of human SPLUNC1 and LPLUNC1 mRNA abundance in various human tissues samples. Relative expression was determined by the ΔΔCt method using human GUS-B RNA as a control. (mean ± S.D., n = 3). Human SPLUNC1 is highly expressed in tissues from nasal, laryngeal, pharyngeal, tracheal, and bronchial regions.

Figure 2. SPLUNC1 and lysozyme were co-localized in a subset of serous cells in SMGs

Cellular localization of SPLUNC1 (A) and lysozyme (B) proteins was assessed by immuno-histochemistry on lung sections of human trachea. Signal was not detected when parallel sections were incubated with pre-immune serum (data not shown). Original magnification, 100X.