Submitted on January 6, 2004
Accepted on December 14, 2004
Parotid secretory protein (PSP) is an HDL-associated protein with anticandidal activity
Weerapan Khovidhunkit1, Jean Pierre Hachem2, Katalin F Medzihradszky3, Philippe N Duchateau4, Judy K Shigenaga5, Arthur H Moser5, Irina Movsesyan4, Josefina Naya-Vigne4, John P Kane6, Kenneth R Feingold7, and Carl Grunfeld1*
1 Metabolism Section, Medical Service, Department of Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA
2 Dermatology Service, Department of Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, CA, USA
3 Department of Pharmaceutical Chemistry and Mass Spectrometry Facility, University of California, San Francisco, San Francisco, CA, USA
4 Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA
5 Metabolism Section, Medical Service, Department of Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, CA, USA
6 Department of Medicine, University of California, San Francisco, San Francisco, CA, USA; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA
7 Metabolism Section, Medical Service, Department of Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA; Dermatology Service, Department of Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, CA, USA
* To whom correspondence should be addressed. E-mail: grunfld{at}itsa.ucsf.edu.
High-density lipoprotein (HDL) is part of innate immunity, protecting against infection and inflammation. Using a proteomic approach, we identified an amino acid sequence in a hamster HDL protein that showed homology to rat and mouse parotid secretory protein (PSP), a salivary protein secreted from the parotid glands. We cloned the cDNA encoding a putative hamster homologue of rat and mouse PSP. Searches for conserved domains of the protein
showed that the carboxy terminus of hamster PSP contains a region homologous to the amino termini of a family of HDL-associated proteins, including lipopolysaccharide binding protein (LBP), cholesteryl ester transfer protein (CETP), and phospholipid transfer protein (PLTP). In mice, PSP was also associated with HDL, but was not detected in very low-density lipoprotein, low-density lipoprotein, or lipoprotein-deficient sera. In addition to salivary glands, we found that PSP mRNA was expressed in lung, testis, and ovary. The level of PSP in HDL was increased after endotoxin injection in hamsters, but not in mice. Recombinant PSP inhibits growth of Candida albicans in culture. In summary, our results showed that PSP is a novel
anticandidal protein associated with HDL.
