Regulation of corneal inflammation by neutrophil-dependent cleavage of keratan sulfate proteoglycans as a model for breakdown of the chemokine gradient

Eric C. Carlson, Yan Sun, Jeffery Auletta, Winston W Y Kao, Chia Yang Liu, Victor L Perez Quinones, Eric Pearlman

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Keratocan and lumican are small, leucine-rich repeat KSPGs in the extracellular matrix (ECM) of the mammalian cornea, whose primary role is to maintain corneal transparency. In the current study, we examined the role of these proteoglycans in the breakdown of the chemokine gradient and resolution of corneal inflammation. LPS was injected into the corneal stroma of C57BL/6 mice, and corneal extracts were examined by immunoblot analysis. We found reduced expression of the 52-kD keratocan protein after 6 h and conversely, increased expression of 34/37 kD immunoreactive products. Further, appearance of the 34/37-kD proteins was dependent on neutrophil infiltration to the cornea, as the appearance of these products was coincident with neutrophil infiltration, and the 34/37-kD products were not detected in explanted corneas or in CXCR2 -/- corneas with deficient neutrophil recruitment. Furthermore, the 34/37-kD products and CXCL1/KC were detected in the anterior chamber, into which the corneal stroma drains; and CXCL1/KC was elevated significantly in keratocan-/- and lumican-/- mice. Together, these findings indicate that the inflammatory response in the cornea is regulated by proteoglycan/CXCL1 complexes, and their diffusion into the anterior chamber is consistent with release of a chemokine gradient and resolution of inflammation.

Original languageEnglish
Pages (from-to)517-522
Number of pages6
JournalJournal of Leukocyte Biology
Volume88
Issue number3
DOIs
StatePublished - Sep 1 2010

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Keratan Sulfate
Proteoglycans
Chemokines
Cornea
Neutrophils
Neutrophil Infiltration
Inflammation
Corneal Stroma
Anterior Chamber
Inbred C57BL Mouse
Leucine
Extracellular Matrix
Proteins

Keywords

  • Extracellular matrix
  • Keratitis
  • Matrix metalloproteinase

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

Cite this

Regulation of corneal inflammation by neutrophil-dependent cleavage of keratan sulfate proteoglycans as a model for breakdown of the chemokine gradient. / Carlson, Eric C.; Sun, Yan; Auletta, Jeffery; Kao, Winston W Y; Liu, Chia Yang; Perez Quinones, Victor L; Pearlman, Eric.

In: Journal of Leukocyte Biology, Vol. 88, No. 3, 01.09.2010, p. 517-522.

Research output: Contribution to journalArticle

Carlson, Eric C. ; Sun, Yan ; Auletta, Jeffery ; Kao, Winston W Y ; Liu, Chia Yang ; Perez Quinones, Victor L ; Pearlman, Eric. / Regulation of corneal inflammation by neutrophil-dependent cleavage of keratan sulfate proteoglycans as a model for breakdown of the chemokine gradient. In: Journal of Leukocyte Biology. 2010 ; Vol. 88, No. 3. pp. 517-522.
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