Localization of the angiogenesis inhibitor thrombospondin in human synovial tissues

Alisa E. Koch, Jon Friedman, James C. Burrows, George K. Haines, Noel P. Bouck

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38 Scopus citations

Abstract

Recently, we have shown that a macrophage subpopulation isolated from the synovial tissue of patients with rheumatoid arthritis was potently angiogenic and that a secreted inhibitor of angiogenesis. which is controlled by a tumor suppressor gene in hamster cells, was similar to thrombospondin. In order to investigate the potential role of thrombospondin in human arthritic disorders, we employed immunohistochemistry to examine frozen synovial tissue sections from normal controls (n = 3), patients with rheumatoid arthritis (n = 14) and with osteoarthritis (n = 5). The synovial tissues were stained with monoclonal antibody (mAb) A2.5, which reacts with the heparin-binding domain of thrombospondin. mAb A6.1. which reacts with the epidermal growth factor repeat motif of thrombospondin. and with mAb A4.1, which reacts with the properdin-repeat domain of thrombospondin. In rheumatoid synovial tissues the anti-thrombospondin mAbs reacted with vascular endothelial cells, and to a lesser extent with vascular smooth muscle. Pericytes were stained, particularly with mAb 6.1. Reactivity was also found with isolated macrophages and with the macrophage-derived synovial lining layer in over half the tissues. In osteoarthritis synovial tissues, mAb A2.5 stained fewer macrophages than in rheumatoid arthritis synovial tissues. Slightly fewer blood vessels reacted with mAb A2.5 in normal compared to diseased synovia. The mAbs reacted with capillaries. venules and arterioles in all synovial tissues. We conclude that mAbs to thrombospondin react primarily with blood vessels and macrophages in synovial tissues. Perhaps thrombospondin may function as an adhesive glycoprotein mediating cellular interactions, or it may serve to counteract the effects of the angiogenic factors produced by cells within diseased synovial tissues.

Original languageEnglish
Pages (from-to)1-6
Number of pages6
JournalPathobiology
Volume61
Issue number1
DOIs
StatePublished - 1993
Externally publishedYes

Keywords

  • Angiogenesis inhibitor
  • Cellular adhesion
  • Rheumatoid arthritis
  • Thrombospondin

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