Effects of tumor necrosis factor-alpha, interleukin 1beta, and activated peripheral blood mononuclear cells on the expression of adhesion molecules and recruitment of leukocytes in rheumatoid synovial xenografts in SCID mice

Abstract

Objective: To examine expression of adhesion molecules within human synovial xenografts in vivo after injection of human cytokines or peripheral blood mononuclear cells (PBMC).

Methods: Rheumatoid synovium was transplanted into subcutaneous pouches in the ears of severe combined immunodeficient (SCID) mice. Tumor necrosis factor-alpha (TNF-alpha), interleukin 1beta (IL-1beta), or PBMC were injected into the xenografts. The grafts were assessed by immunohistochemistry and quantitative video image analysis.

Results: TNF-alpha, IL-1beta, and concanavalin A activated PBMC increased the expression of vascular cellular adhesion molecule 1 and intercellular adhesion molecule 1 significantly on vessels and nonvascular synovial cells compared with injection of medium only. Vascular expression of E-selectin, but not of MHC Class II, was also increased. These stimuli also induced the migration of murine leukocytes into the xenografts.

Conclusion: Rheumatoid synovial xenografts in SCID mice respond by upregulation of adhesion molecule expression when challenged in vivo with proinflammatory cytokines or activated PBMC.