Keratocan and lumican regulate neutrophil infiltration and corneal clarity in lipopolysaccharide-induced keratitis by direct interaction with CXCL1.

Published

Journal Article

Keratocan and lumican are keratan-sulfate proteoglycans (KSPG), which have a critical role in maintaining corneal clarity. To determine whether these KSPGs have a role in corneal inflammation, we examined Kera(-/-) and Lum(-/-) mice in a model of lipopolysaccharide (LPS)-induced keratitis in which wild-type mice develop increased corneal thickness and haze due to neutrophil infiltration to the corneal stroma. Corneal thickness increases caused by LPS mice were significantly lower in Kera(-/-) and Lum(-/-) than wild-type mice. Further, LPS-injected Lum(-/-) mice had elevated corneal haze levels compared with that of Kera(-/-) and wild-type. At 24 h post-injection, total enhanced green fluorescent protein-positive bone marrow-derived inflammatory cells in chimeric mice was significantly lower in Kera(-/-) mice and Lum(-/-) mice compared with wild-type mice. Neutrophil infiltration was inhibited in Kera(-/-) and Lum(-/-) mice at 6 and 24 h post-stimulation, with Lum(-/-) corneas having the most profound defect in neutrophil migration. Reconstitution of keratocan and lumican expression in corneas of Kera(-/-) and Lum(-/-) mice using adeno-keratocan and adeno-lumican viral vectors, respectively, resulted in normal neutrophil infiltration in response to LPS. Immunoprecipitation/Western blot analysis showed that lumican and keratocan core proteins bind the CXC chemokine KC during a corneal inflammatory response, indicating that corneal KSPGs mediate neutrophil recruitment to the cornea by regulating chemokine gradient formation. Together, these data support a significant role for lumican and keratocan in a corneal inflammatory response with respect to edema, corneal clarity, and cellular infiltration.

Full Text

Duke Authors

Cited Authors

  • Carlson, EC; Lin, M; Liu, C-Y; Kao, WW-Y; Perez, VL; Pearlman, E

Published Date

  • December 7, 2007

Published In

Volume / Issue

  • 282 / 49

Start / End Page

  • 35502 - 35509

PubMed ID

  • 17911102

Pubmed Central ID

  • 17911102

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.M705823200

Language

  • eng

Conference Location

  • United States