Expression of chemokines and gelatinase B in sympathetic ophthalmia

Abstract

Purpose To examine the expression of gelatinase B (matrix metalloproteinase-9) and the chemokines monocyte chemotactic protein-1 (CCL2/MCP-1) and stromal cell-derived factor-1 (CXCL12/SDF-1) in sympathetic ophthalmia (SO). Methods Five enucleated exciting eyes with a clinical diagnosis and typical histopathological findings of SO were studied by immunohistochemical techniques using a panel of monoclonal antibodies directed against gelatinase B, MCP-1, and SDF-1. In addition, a panel of monoclonal and polyclonal antibodies was used to characterize the composition of the inflammatory infiltrate. Results In all cases, the extensive uveal inflammatory infiltrate was organized as a diffuse infiltrate and as large granulomas consisting of epithelioid cells and multinucleated giant cells. CD20 þ B lymphocytes predominated in the diffuse infiltrate and CD3 þ T lymphocytes were few. The monocyte/macrophage marker CD68 was expressed in scattered inflammatory mononuclear cells and within granulomas and Dalen-Fuchs nodules. Most of the inflammatory cells were HLA-DR þ . Immunoreactivity for gelatinase B, MCP-1, and SDF-1 was observed in cells within granulomas and in scattered epithelioid cells. Immunoreactivity for MCP-1 was noted in retinal pigment epithelial cells. Endothelial cells of choriocapillaries showed weak immunoreactivity for SDF-1. Conclusions Gelatinase B, MCP-1, and SDF-1 might have a pathogenic role in the recruitment of leucocytes into the eye in SO.

Differential CXC and CX3C Chemokine Expression Profiles in Aqueous Humor of Patients With Specific Endogenous Uveitic Entities

“…1,2 Inflammatory chemokines are secreted proteins that recruit leukocytes from blood to sites of inflammation via activation of 7-transmembrane-domain G-protein-coupled receptors. 3 Evidence is accumulating that chemokine and chemokine receptor antagonists have strong therapeutic potential for autoimmune diseases.…”

The Role of Perivascular Melanophage Infiltrates in the Conjunctiva in Sympathetic Ophthalmia

“…The cellular components identified in the current case were similar to those previously described in the uveal tract in cases of SO. These included an increase in CD3 + (T cell receptor marker) and CD4 + cells (T-cell receptor that aids adherence of T cells to HLA-DR antigen presenting cells), 11, 12 CD68 + melanophages, 12 and increased numbers of HLA-DR-labeled cells. 11,12 The observation of subconjunctival melanophages in the presence of uveal prolapse is not surprising.…”

“…These included an increase in CD3 + (T cell receptor marker) and CD4 + cells (T-cell receptor that aids adherence of T cells to HLA-DR antigen presenting cells), 11, 12 CD68 + melanophages, 12 and increased numbers of HLA-DR-labeled cells. 11,12 The observation of subconjunctival melanophages in the presence of uveal prolapse is not surprising. However, such pigment-laden cells may be mistaken for migrating uveal melanocytes based on morphology, and the literature often refers to these pigmented cells as "uveal pigment" and does not discern melanocytes from macrophages.…”

“…In addition to the eliciting antigens, there are also several chemokines, enzymes (gelatinase B), and tyrosinase-like molecules that mediate the complex immune response and antigen processing by the macrophages. 6,12 The limitation of our unique observation is that it is restricted to examination of specimens from a single case with limited tissue in a relatively rare disease, which also prevents us from exploring the role of these other molecules that may play a role in the complex process of antigen presentation and autoimmunity. 23 …”

The role of chemokines and their receptors in uveitis

“…Endothelial cells of choriocapillaris had weak immunoreactivity for SDF-1. These findings suggest MCP-1 and SDF-1 might have a pathogenic role in the recruitment of leukocytes into the eye in sympathetic ophthalmia [44].…”