High expression of chemokines Gro-alpha (CXCL-1), IL-8 (CXCL-8), and MCP-1 (CCL-2) in inflamed human corneas in vivo

Arch Ophthalmol. 2003 Jun;121(6):825-31. doi: 10.1001/archopht.121.6.825.

Abstract

Objective: To investigate in vivo expression of chemokines in normal and inflamed human corneas, to determine whether chemokines are responsible for the recruitment of inflammatory cells.

Methods: In situ hybridization of the CXC chemokines growth-related oncogene-alpha (Gro-alpha) (CXCL-1), interleukin 8 (CXCL-8), macrophage interferon-gamma inducible gene (CXCL-9), and interferon-gamma inducible protein 10 (CXCL-10) and of the CC chemokines macrophage chemoattractant protein 1 (MCP-1) (CCL-2), macrophage inflammatory protein 1alpha (CCL-3), and regulated on activation, normal T-cell expressed and secreted (CCL-5) was performed to localize chemokine messenger RNA. Immunohistochemistry was used to identify the cellular infiltrate within the cornea. Three normal human eyes were compared with eyes enucleated because of chronic inflammation (n = 10), secondary to perforating injuries.

Results: In normal corneas, no chemokine expression was detected. In inflamed lesions, a high intensity of signals from Gro-alpha (CXCL-1) and MCP-1 (CCL-2) messenger RNA was observed in limbal epithelium and from Gro-alpha (CXCL-1), interleukin 8 (CXCL-8), and MCP-1 (CCL-2) in corneal stroma. The Gro-alpha (CXCL-1) was the only chemokine expressed by central corneal epithelium. All other examined chemokines were only moderately expressed in limbus and corneal stroma, or barely detectable.

Conclusions: These cytokines are important agents in the cytokine network and contribute to the cell-specific and spatially restricted recruitment of neutrophils and mononuclear cells in acute inflammatory lesions of the human cornea. Clinical Relevance Understanding the role of chemokines in corneal inflammation may lead to the development of a selective receptor blockage of highly expressed chemokines to inhibit the recruitment of leukocyte subsets.

MeSH terms

  • Antibodies, Monoclonal
  • Chemokine CCL2 / genetics*
  • Chemokine CCL2 / metabolism
  • Chemokine CCL4
  • Chemokine CXCL1
  • Chemokine CXCL10
  • Chemokine CXCL9
  • Chemokines / genetics*
  • Chemokines / metabolism
  • Chemokines, CXC / genetics
  • Chemokines, CXC / metabolism
  • Chemotactic Factors / genetics*
  • Chemotactic Factors / metabolism
  • Cornea / metabolism
  • Eye Injuries, Penetrating / complications
  • Eye Injuries, Penetrating / metabolism
  • Humans
  • Immunoenzyme Techniques
  • In Situ Hybridization
  • Inflammation
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Interleukin-8 / genetics*
  • Interleukin-8 / metabolism
  • Keratitis / etiology
  • Keratitis / metabolism*
  • Langerhans Cells / physiology
  • Macrophage Inflammatory Proteins / genetics
  • Macrophage Inflammatory Proteins / metabolism
  • Macrophages / physiology
  • Neutrophils / physiology
  • RNA, Messenger / metabolism
  • T-Lymphocytes / physiology

Substances

  • Antibodies, Monoclonal
  • CXCL1 protein, human
  • CXCL9 protein, human
  • Chemokine CCL2
  • Chemokine CCL4
  • Chemokine CXCL1
  • Chemokine CXCL10
  • Chemokine CXCL9
  • Chemokines
  • Chemokines, CXC
  • Chemotactic Factors
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-8
  • Macrophage Inflammatory Proteins
  • RNA, Messenger