Histopathology of the rheumatoid lesion

Abstract

Histochemical and ultrastructural techniques were used to examine the cartilage-pannus junction of 49 rheumatoid joints. Whereas 24 showed relatively acellular, fibrous pannus tissue, 25 demonstrated "cellular" junctions with different cell types at sites of erosion. Macrophages and fibroblasts were commonly observed as majority cell types in most specimens, but others showed mast cells, polymorphonuclear leukocytes, dendritic, or plasma cells as the predominant cell type. Some showed local accumulations of different cell types at sites along each junction. Our findings show that the cellular composition at sites of cartilage erosion varies greatly and suggest that cells are subject to turnover and interchange.Extensive proteolytic degradation of articular cartilage is a characteristic feature of joint destruction in rheumatoid arthritis. This process is generally irreversible and is commonly associatcd with invasive, hypertrophied synovium. Histologic observations have shown that the early rheumatoid lesion is characterized by a proliferation of synovial lining cells with subscquent neovascularization and infiltration by lym-

Interleukin‐4 stimulates rheumatoid synovial fibroblasts to express matrix metalloproteinase‐1 (tissue collagenase) and histamine H1 receptor mRNA

“…RA is an inflammatory joint disease associated with pronounced infiltration of various types of inflammatory ceils including mast cells and mononuclear cells (1,2). Various researchers have reported increased levels of cytokines and histamine in RA synovial fluid (8,(19)(20)(21).…”

“…In rheumatoid arthritis (RA), the synovial tissue reveals a proliferation of synovial fibroblasts with an infiltration of various types of inflammatory cells including mast cells and mononuclear cells (1,2). This results in destructive joint changes thought to be driven by a variety of events such as cell secretion, cell-cell interaction, and degradation of the extracellular matrix.…”

Mast cell proteinases activate precursor forms of collagenase and stromelysin, but not of gelatinases A and B

“…All the metalloproteinases are secreted as precursor forms requiring extracellular activation prior to substrate attack. Activation of the pro- ~-enzymes has been demonstrated in vitro by proteolytic cleavage of their propeptide domains and also by organomercurial compounds such as aminophenyl mercuric acetate (H,NPhHgAc) [2, 4-61, but the activation mechanisms that function in vivo remain unclear.Since mast cells are commonly associated with sites of connective-tissue lysis, for example at sites of tumour invasion in melanoma and breast carcinoma [7, 81 and at cartilage erosion sites in rheumatoid arthritis [9], a potential role for this cell in matrix degradation has been proposed [7, 101. Previous reports showed that mast cell extracts were capable of activating latent collagenase [ l l ] and mast cell tryptase of activating prostromelysin [12].…”

“…Since mast cells are commonly associated with sites of connective-tissue lysis, for example at sites of tumour invasion in melanoma and breast carcinoma [7, 81 and at cartilage erosion sites in rheumatoid arthritis [9], a potential role for this cell in matrix degradation has been proposed [7, 101. Previous reports showed that mast cell extracts were capable of activating latent collagenase [ l l ] and mast cell tryptase of activating prostromelysin [12].…”

“…All the metalloproteinases are secreted as precursor forms requiring extracellular activation prior to substrate attack. Activation of the pro- Since mast cells are commonly associated with sites of connective-tissue lysis, for example at sites of tumour invasion in melanoma and breast carcinoma [7,81 and at cartilage erosion sites in rheumatoid arthritis [9], a potential role for this cell in matrix degradation has been proposed [7, 101. Previous reports showed that mast cell extracts were capable of activating latent collagenase [ l l ] and mast cell tryptase of activating prostromelysin [12]. Here we report the effects of mast cell proteinases on four purified metalloproteinases, procollagenase (pMMP-l), progelatinase A (pMMP-2), prostromelysin (pMMP-3) and progelatinase B (pMMP-9).…”