| First Author | Shao H | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 43 | Pages | 35860-72 |
| PubMed ID | 22865855 | Mgi Jnum | J:191593 |
| Mgi Id | MGI:5462144 | Doi | 10.1074/jbc.M112.380550 |
| Citation | Shao H, et al. (2012) Extracellular matrix lumican promotes bacterial phagocytosis, and Lum-/- mice show increased Pseudomonas aeruginosa lung infection severity. J Biol Chem 287(43):35860-72 |
| abstractText | 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 (MPhis). Lumican co-localized with CD14, CD18, and bacteria on Lum(+/+) MPhi 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(-/-) MPhis. Surface plasmon resonance showed specific binding of rLum to CD14 (K(A) = 2.15 x 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(-/-) MPhis, 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. |
