Icam-1: A Signaling Molecule For Immune-based Inflammtion In Dry Eye Patients And Mrl/lpr Mice

Abstract

Abstract: : Purpose: We have previously reported that immune-based inflammation occurs on the ocular surface of humans and canines with keratoconjunctivitis sicca (KCS). Intercellular adhesion molecule-1 (ICAM-1) was found to be over-expressed on lymphocytes and/or vascular endothelial cells resulting in lymphocytic diapedesis to the lacrimal and conjunctival tissues. The purpose of the current study is to demonstrate whether epithelial cells on the ocular surface (OS) are capable of actively producing ICAM-1 in the immune-based inflammatory process. Additionally, we sought to determine whether the lymphocytic accumulation in the targeted ocular tissues is the result of local lymphocyte proliferation, or infiltrating lymphocytes from peripheral circulation. Methods: ICAM-1 expression in various ocular tissues of human with KCS and/or MRL/lpr mouse was evaluated by immunohistochemistry and in situ hybridization at the protein and message level respectively. ELISA was carried out to measure plasma soluble ICAM-1 concentrations in MRL/lpr mouse over time. Cell proliferation within ocular tissues was assessed by bromodeoxyuridine (BrdU) incorporation and immunohistochemical detection. The level of T cell activation was determined by IL-2 receptor immunoreactivity using FACS analysis. Results: Increased endogenous ICAM-1 at the level of protein and messenger RNA was detected in the epithelial cells in the conjunctival and accessory lacrimal tissues in dry eye patients. Mean sICAM-1 level was markedly higher over time compared with the controls. No significant lymphocytic proliferation or T cell activation was detected within the lacrimal glands of MRL/lpr mice. Conclusion: Our findings suggest that ICAM-1 up-regulation locally and systemically promote lymphocyte activation and migration to the ocular surface and facilitates potential antigen presentation by epithelial cells. OS epithelium is an active component and may interact with invasive lymphocytes by producing ICAM-I in response to immune activation and inflammation. Lymphocytic infiltrates in the local ocular tissues are likely from the circulation instead of local T cell proliferation in the lacrimal gland.

Keywords: 452 lacrimal gland • 437 inflammation • 339 cell adhesions/cell junctions