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

Publication ,  Journal Article
Carlson, EC; Lin, M; Liu, C-Y; Kao, WW-Y; Perez, VL; Pearlman, E
Published in: J Biol Chem
December 7, 2007

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.

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Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

December 7, 2007

Volume

282

Issue

49

Start / End Page

35502 / 35509

Location

United States

Related Subject Headings

  • Transduction, Genetic
  • Time Factors
  • Proteoglycans
  • Protein Binding
  • Neutrophils
  • Neutrophil Infiltration
  • Mice, Knockout
  • Mice
  • Lumican
  • Lipopolysaccharides
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Carlson, E. C., Lin, M., Liu, C.-Y., Kao, W.-Y., Perez, V. L., & Pearlman, E. (2007). Keratocan and lumican regulate neutrophil infiltration and corneal clarity in lipopolysaccharide-induced keratitis by direct interaction with CXCL1. J Biol Chem, 282(49), 35502–35509. https://doi.org/10.1074/jbc.M705823200
Carlson, Eric C., Michelle Lin, Chia-Yang Liu, Winston W-Y Kao, Victor L. Perez, and Eric Pearlman. “Keratocan and lumican regulate neutrophil infiltration and corneal clarity in lipopolysaccharide-induced keratitis by direct interaction with CXCL1.J Biol Chem 282, no. 49 (December 7, 2007): 35502–9. https://doi.org/10.1074/jbc.M705823200.
Carlson EC, Lin M, Liu C-Y, Kao WW-Y, Perez VL, Pearlman E. Keratocan and lumican regulate neutrophil infiltration and corneal clarity in lipopolysaccharide-induced keratitis by direct interaction with CXCL1. J Biol Chem. 2007 Dec 7;282(49):35502–9.
Carlson, Eric C., et al. “Keratocan and lumican regulate neutrophil infiltration and corneal clarity in lipopolysaccharide-induced keratitis by direct interaction with CXCL1.J Biol Chem, vol. 282, no. 49, Dec. 2007, pp. 35502–09. Pubmed, doi:10.1074/jbc.M705823200.
Carlson EC, Lin M, Liu C-Y, Kao WW-Y, Perez VL, Pearlman E. Keratocan and lumican regulate neutrophil infiltration and corneal clarity in lipopolysaccharide-induced keratitis by direct interaction with CXCL1. J Biol Chem. 2007 Dec 7;282(49):35502–35509.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

December 7, 2007

Volume

282

Issue

49

Start / End Page

35502 / 35509

Location

United States

Related Subject Headings

  • Transduction, Genetic
  • Time Factors
  • Proteoglycans
  • Protein Binding
  • Neutrophils
  • Neutrophil Infiltration
  • Mice, Knockout
  • Mice
  • Lumican
  • Lipopolysaccharides