Extracellular matrix lumican promotes bacterial phagocytosis, and Lum-/- mice show increased Pseudomonas aeruginosa lung infection severity

J Biol Chem. 2012 Oct 19;287(43):35860-72. doi: 10.1074/jbc.M112.380550. Epub 2012 Aug 3.


Phagocytosis is central to bacterial clearance, but the exact mechanism is incompletely understood. Here, we show a novel and critical role for lumican, the connective tissue extracellular matrix small leucine-rich repeat proteoglycan, in CD14-mediated bacterial phagocytosis. In Psuedomonas aeruginosa lung infections, lumican-deficient (Lum(-/-)) mice failed to clear the bacterium from lungs, tissues, and showed a dramatic increase in mortality. In vitro, phagocytosis of nonopsonized gram-negative Escherichia coli and P. aeruginosa was inhibited in Lum(-/-) peritoneal macrophages (MΦs). Lumican co-localized with CD14, CD18, and bacteria on Lum(+/+) MΦ surfaces. Using two different P. aeruginosa strains that require host CD14 (808) or CD18/CR3 (P1) for phagocytosis, we showed that lumican has a larger role in CD14-mediated phagocytosis. Recombinant lumican (rLum) restored phagocytosis in Lum(-/-) MΦs. Surface plasmon resonance showed specific binding of rLum to CD14 (K(A) = 2.15 × 10(6) M(-1)), whereas rLumY20A, and not rLumY21A, where a tyrosine in each was replaced with an alanine, showed 60-fold decreased binding. The rLumY20A variant also failed to restore phagocytosis in Lum(-/-) MΦs, indicating Tyr-20 to be functionally important. Thus, in addition to a structural role in connective tissues, lumican has a major protective role in gram-negative bacterial infections, a novel function for small leucine-rich repeat proteoglycans.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Substitution
  • Animals
  • CD18 Antigens / genetics
  • CD18 Antigens / immunology
  • CD18 Antigens / metabolism
  • Chondroitin Sulfate Proteoglycans / genetics
  • Chondroitin Sulfate Proteoglycans / immunology*
  • Chondroitin Sulfate Proteoglycans / metabolism
  • Keratan Sulfate / genetics
  • Keratan Sulfate / immunology*
  • Keratan Sulfate / metabolism
  • Lipopolysaccharide Receptors / genetics
  • Lipopolysaccharide Receptors / immunology
  • Lipopolysaccharide Receptors / metabolism
  • Lumican
  • Macrophages, Peritoneal / immunology*
  • Macrophages, Peritoneal / metabolism
  • Macrophages, Peritoneal / microbiology
  • Mice
  • Mice, Knockout
  • Mutation, Missense
  • Phagocytosis / immunology*
  • Pneumonia, Bacterial / genetics
  • Pneumonia, Bacterial / immunology*
  • Pneumonia, Bacterial / metabolism
  • Pseudomonas Infections / genetics
  • Pseudomonas Infections / immunology*
  • Pseudomonas Infections / metabolism
  • Pseudomonas aeruginosa / immunology*


  • CD18 Antigens
  • Chondroitin Sulfate Proteoglycans
  • Lipopolysaccharide Receptors
  • Lum protein, mouse
  • Lumican
  • Keratan Sulfate