Electron microscopic observations of immunoreactive cells in the rheumatoid synovial membrane

Ishikawa, Hitoshi; Ziff, Morris

doi:10.1002/art.1780190101

Cited by 138 publications

(46 citation statements)

References 27 publications

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“…6 shows the close relationship between CD3 ϩ T cells and intimal lining cells. This is in line with the previously reported association between lymphocytes and FLS (40). Th1 cytokine receptors are known to be expressed on the FLS cell surface.…”

Section: Discussionsupporting

confidence: 92%

Functional IL-2 Receptor β (CD122) and γ (CD132) Chains Are Expressed by Fibroblast-Like Synoviocytes: Activation by IL-2 Stimulates Monocyte Chemoattractant Protein-1 Production

Corrigall

Arastu

Khan

et al. 2001

The Journal of Immunology

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The expression of the IL-2R α-, β-, and γ-chains, CD25, CD122, and CD132, respectively, was investigated on fibroblast-like synoviocytes (FLS) and dermal fibroblasts (DF). Both protein and mRNA for CD122 and CD132 were observed but there was no evidence of CD25 expression. Quantification of the Ag binding sites for CD122 showed that FLS expressed 4 times more receptor molecules than DF. The functional capability of these receptors was confirmed by the production of monocyte chemoattractant protein-1 (MCP-1) in direct response to stimulation by IL-2, which could be inhibited by neutralizing anti-CD122 mAb. Both rheumatoid arthritis (RA) and osteoarthritis (OA) FLS and DF spontaneously produced MCP-1 in culture over a similar range of concentrations. However, RA and OA FLS produced significantly greater levels of MCP-1 following stimulation by IL-2 and IL-1β; RA FLS produced significantly more MCP-1 than OA FLS. Addition of exogenous IL-2 caused a slight, but significant, decrease in MCP-1 production by DF. The addition of neutralizing anti-CD122 mAb to FLS cultures partially, but significantly, reduced the IL-2-induced MCP-1 secretion, but did not effect either the spontaneous or IL-1β-induced secretion of MCP-1. Increased tyrosine phosphorylation was observed in FLS lysates following 30-min incubation with IL-2. In conclusion, in the inflamed synovium, as activated T cells migrate through the sublining and lining layer, T cell-derived IL-2 may activate FLS to secrete MCP-1, thus recruiting macrophages into the rheumatoid synovium and perpetuating inflammation.

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Section: Discussionsupporting

confidence: 92%

Functional IL-2 Receptor β (CD122) and γ (CD132) Chains Are Expressed by Fibroblast-Like Synoviocytes: Activation by IL-2 Stimulates Monocyte Chemoattractant Protein-1 Production

Corrigall

Arastu

Khan

et al. 2001

The Journal of Immunology

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“…Clear cytoplasm contains numerous small vesicles and narrow tubules, whorl-shaped endoplasmic reticulum (arrowheads), and few lysosomes (original magnification x 3,300). areas have been described (23,30,31). We have examined the reactions of monoclonal antibodies with the cell membranes of the mononuclear cells in these areas and rn the lining and interstitial areas of the synovium, by use of an immunoelectron microscopic method.…”

Section: Discussionmentioning

confidence: 99%

Electron microscopic study of HLA‐DR and monocyte/macrophage staining cells in the rheumatoid synovial membrane

Iguchi

Kurosaka

Ziff

1986

Arthritis & Rheumatism

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We examined synovial membrane samples from 6 rheumatoid arthritis (RA) and 3 osteoarthritis patients and from 1 normal subject, by an immunoelectron microscopic technique using anti-HLA-DR (anti-Ia) and anti-monocyte/macrophage (63D3) monoclonal antibodies. In the lining layer, the type A macrophage-like cells were strongly DR+ and 63D3+, whereas the type B fibroblast-like cells were almost completely negative. Lymphocyte-rich areas (containing more than 90% densely packed lymphocytes) showed weak and patchy DR staining of the lymphocytes. In these areas, 3 4 % of the cells were macrophage-like cells which were 63D3-, a type of staining compatible with that of the interdigitating cell (IDC). In the plasma cell-containing (transitional) areas, many strongly DR+ macrophage-like cells were observed in close contact with lymphocytes and plasma cells. Ten to twenty percent of these cells were 63D3-, which suggests that they were IDC. Cells with the structural appearance of IDC were most frequently seen in those transitional areas which contained elevated concentrations (50-70%) of lymphocytes. In uninfiltratFrom the Harold C.

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“…The patient's age, however, affected the thickness of the BM, in that the BMW, BMWR, and FBMA of each of the 3 types of synovial areas were significantly higher in patients over the age of 50 than in patients under age 50. Since transitional areas are populated by macrophages, lymphocytes, plasmablasts, and plasma cells, these areas may be considered to be the most immunologically active areas of RA synovium (17). Such are the areas in which the secretion of antibodies and of the cytokines of lymphocytes and macrophages may be expected to take place.…”

Section: #mentioning

confidence: 99%

Basement membrane thickening of postcapillary venules and capillaries in rheumatoid synovium

Matsubara

Ziff

Smith

1987

Arthritis & Rheumatism

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Pathologic changes in the basement membrane (BM) of postcapillary venules (PCV) and capillaries in rheumatoid arthritis (RA) synovium were studied by immunoelectron microscopy, using a monoclonal antibody against human type IV collagen, C(IV)22, and by electron microscopic morphometric analysis. The sublining region of RA synovium was classified into lymphocyte‐rich areas, transitional areas, and interstitial areas, according to their pattern of cellular infiltration. In lymphocyte‐rich areas, the BM of the PCV and capillaries were minimally thickened; disruption of the lamina densa was seldom seen. Transitional areas, which contained macrophages, lymphocytes, and plasma cells, had numerous PCV and capillaries. The BM was markedly thickened and partially multilamellated, and there were many disruptions in the lamina densa. The BM contained degenerated endothelial cells and cell debris. On immunostaining of this BM with monoclonal antibody C(IV)22, type IV collagen stained heavily, mainly in the disrupted lamina densa; this indicates that the thickening was, at least in part, the result of an increase in BM collagen. In uninfiltrated interstitial areas, BM were moderately thickened and multilamellated, and showed few disruptions of the lamina densa; there were similar increases in type IV collagen, but cell debris was seldom observed. Measurement of the BM width, the ratio of BM width to vessel diameter, and the fraction of vascular cross‐sectional area occupied by BM demonstrated that the thickness of the BM of both PCV and capillaries was greatest in transitional areas and was smallest in lymphocyte‐rich areas (P <0.01). Since macrophages and macrophage‐derived factors have been found to promote synthesis of BM collagen type IV, and since transitional and interstitial areas are rich in macrophages and histiocytes, respectively, it is suggested that these mononuclear cells and the factors secreted by them play a significant role in the thickening of the BM of PCV and capillaries in RA synovitis.

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Electron microscopic observations of immunoreactive cells in the rheumatoid synovial membrane

Cited by 138 publications

References 27 publications

Functional IL-2 Receptor β (CD122) and γ (CD132) Chains Are Expressed by Fibroblast-Like Synoviocytes: Activation by IL-2 Stimulates Monocyte Chemoattractant Protein-1 Production

Functional IL-2 Receptor β (CD122) and γ (CD132) Chains Are Expressed by Fibroblast-Like Synoviocytes: Activation by IL-2 Stimulates Monocyte Chemoattractant Protein-1 Production

Electron microscopic study of HLA‐DR and monocyte/macrophage staining cells in the rheumatoid synovial membrane

Basement membrane thickening of postcapillary venules and capillaries in rheumatoid synovium

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