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.
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.


CONCLUSIONS
Rheumatoid synovial xenografts in SCID mice respond by upregulation of adhesion molecule expression when challenged in vivo with proinflammatory cytokines or activated PBMC.
Proudman
S M
SM
Arthritis Research Laboratory, Hanson Center for Cancer Research, Royal Adelaide Hospital, Australia.
Cleland
L G
LG
Mayrhofer
G
G
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D015552:Injections, Intralesional; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism* / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D012680:Sensitivity and Specificity; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism*; D014183:Transplantation, Heterologous; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism*
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1