Importance of beta-2 integrins in endotoxin-induced uveitis as determined in genetically altered mice

Purpose: A variety of adhesion molecules have been implicated in the inflammatory process. Antibody studies have previously implicated β₂ integrins in intraocular inflammation, but antibodies may have inadequate distribution or unanticipated effects from binding to the cell surface. Methods: We studied mice with specific gene deletions for either β₂ integrin or its principal ligand, intercellular adhesion molecule-1 (ICAM-1). Gene deleted mice or congenic controls were injected intravitreally with 250 ng of endotoxin. Results: Scoring inflammation on the basis of the number of leukocytes present in a representative cross-section of the eye, the absence of β₂ integrin significantly reduced the inflammatory infiltrate (168±166 cells/eye section for knockouts vs. 384±212 cells/eye section for controls, (mean ± standard deviation) p < 0.05). In contrast, the absence of ICAM-1 only slightly reduced the leukocytic response (90±140 cells/eye section for knockouts vs. 149±147 cells/eye section for controls, p > 0.1). The reduction in cellular infiltration was 74% in anterior segment, 77% in ciliary body, and 44% in posterior segment for β₂ integrin deficient mice. Conclusion: β₂ integrin contributes to leukocyte migration in endotoxin-induced uveitis but not all cells are dependent on it. ICAM-1 deficient mice also have a reduced cellular infiltrate in endotoxin-induced uveitis, but this difference did not reach statistical significance.