Human Molecular Genetics, 2002, Vol. 11, No. 8 937-943
© 2002 Oxford University Press
PLUNC: A novel family of candidate host defence proteins expressed in the upper airways and nasopharynx
1Respiratory Medicine Unit, Division of Genomic Medicine, University of Sheffield Medical School, Sheffield, S10 2RX, UK and 2Krebs Institute for Biomolecular Research, Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, S10 2TN, UK
The upper respiratory tract, including the nasal and oral cavities, is the major route of entry of pathogens into the body, and early recognition of bacterial products in this region is critical for host defence. A well-established family of four proteins involved in this process are bactericidal/permeability-increasing protein (BPI) and lipopolysaccharide-binding protein (LBP), which are central to the host defence against bacteria, and cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP), which have also been implicated in this response. In this paper, we demonstrate the existence of a related family of seven human proteins, which we designate PLUNC proteins. The PLUNC proteins are encoded by adjacent genes found within a 300 kb region of chromosome 20, suggesting that they may be under transcriptional control of shared genomic elements, and expression data shows that these proteins are found in overlapping regions of the pulmonary, nasopharyngeal and oral epithelium, sites where the previously described BPI family members are not expressed. Whereas the BPI family are predicted to share very closely similar three-dimensional structures, the PLUNC family is predicted to have much greater variability in the N-terminal domain, corresponding to the active domain of BPI, thus creating the notion of a BPI/PLUNC structural superfamily. We suggest that members of the PLUNC family may function in the innate immune response in regions of the mouth, nose and lungs, which are sites of significant bacterial exposure.
* To whom correspondence should be addressed. Tel: +44 0114 271 2638; Fax: +44 0114 272 1104; Email: c.d.bingle{at}sheffield.ac.uk. Correspondence may also be addressed to C. J. Craven. Tel: +44 0114 222 4323; Fax: +44 0114 272 8697; Email: c.j.craven{at}sheffield.ac.uk
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