PLUNC is a novel airway surfactant protein with anti-biofilm activity.
BACKGROUND
The PLUNC ("Palate, lung, nasal epithelium clone") protein is an abundant secretory product of epithelia present throughout the conducting airways of humans and other mammals, which is evolutionarily related to the lipid transfer/lipopolysaccharide binding protein (LT/LBP) family. Two members of this family--the bactericidal/permeability increasing protein (BPI) and the lipopolysaccharide binding protein (LBP)--are innate immune molecules with recognized roles in sensing and responding to Gram negative bacteria, leading many to propose that PLUNC may play a host defense role in the human airways.


RESULTS
Based on its marked hydrophobicity, we hypothesized that PLUNC may be an airway surfactant. We found that purified recombinant human PLUNC greatly enhanced the ability of aqueous solutions to spread on a hydrophobic surface. Furthermore, we discovered that PLUNC significantly reduced surface tension at the air-liquid interface in aqueous solutions, indicating novel and biologically relevant surfactant properties. Of note, surface tensions achieved by adding PLUNC to solutions are very similar to measurements of the surface tension in tracheobronchial secretions from humans and animal models. Because surfactants of microbial origin can disperse matrix-encased bacterial clusters known as biofilms [1], we hypothesized that PLUNC may also have anti-biofilm activity. We found that, at a physiologically relevant concentration, PLUNC inhibited biofilm formation by the airway pathogen Pseudomonas aeruginosa in an in vitro model.


CONCLUSIONS
Our data suggest that the PLUNC protein contributes to the surfactant properties of airway secretions, and that this activity may interfere with biofilm formation by an airway pathogen.
Gakhar
Lokesh
L
Department of Biochemistry and Protein Crystallography Facility, University of Iowa, Iowa City, Iowa, United States of America.
Bartlett
Jennifer A
JA
Penterman
Jon
J
Mizrachi
Dario
D
Singh
Pradeep K
PK
Mallampalli
Rama K
RK
Ramaswamy
S
S
McCray
Paul B
PB
D000595:Amino Acid Sequence; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development*; D002478:Cells, Cultured; D002942:Circular Dichroism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D015151:Immunoblotting; D008168:Lung / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000502:physiology; D011663:Pulmonary Surfactants / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid
C485599:BPIFA1 protein, human; D006023:Glycoproteins; D010750:Phosphoproteins; D011663:Pulmonary Surfactants; D011994:Recombinant Proteins