The effect of genetic deficiency of adhesion molecules on the course of endotoxin-induced uveitis

Stephen R. Planck, Young Bok Han, Jong Moon Park, Leslie O'Rourke, Jose Carlos Gutierrez-Ramos, James T. Rosenbaum

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Purpose. Multiple adhesion molecules of the selectin, integrin, and immunoglobulin-like families are involved in the migration of leukocytes out of the bloodstream into inflamed tissues. This study addresses the question of which adhesion molecules are specifically involved in endotoxin-induced uveitis. Methods. Mice genetically deficient in p-selectin, ICAM-1, β2-integrin, or controls received intravitreal injections of endotoxin. Eyes were harvested 24 h later and inflammation was evaluated by histologic and immunohistochemical assays of infiltrating cells. Results. Mice lacking either P-selectin or β2-integrin had less inflammation than controls (median cells/section: 64 for P-selectin knockout vs 130 for controls, p = 0.02, n = 17 per group; 244 for β2-integrin knockouts, n = 14, vs 355 for controls, n = 17, p = 0.05). Neither gene deletion significantly changed the ratio of infiltrating neutrophils to macrophages. ICAM-1 knockouts tended to have fewer infiltrating cells (median 22 cells/section) compared to controls (median 132 cells/section), but this difference was not statistically significant (p = 0.25, n = 9 per group). Conclusions. P-selectin, β2-integrin, and possibly ICAM-1 are involved in the ocular inflammatory response to endotoxin. The lack of complete inhibition of leukocyte infiltration with the complete loss of each adhesion molecule is in accord with the notion that alternative adhesion molecules also participate in this process.

Original languageEnglish (US)
Pages (from-to)941-946
Number of pages6
JournalCurrent Eye Research
Volume17
Issue number9
DOIs
StatePublished - Sep 29 1998

Keywords

  • Adhesion molecules
  • Endotoxin
  • ICAM-1
  • Mouse
  • P-selectin
  • Targeted gene disruption ('knockout')
  • Uveitis
  • β-integrin

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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