title: Distribution of TNF-alpha, TNF-R55 and TNF-R75 in the rheumatoid synovial membrane: TNF receptors are localized preferentially in the lining layer; TNF-alpha is distributed mainly in the vicinity of TNF receptors in the deeper layers.
abstract: The expression of TNF-alpha and its receptors in the rheumatoid synovial membrane was investigated using immunohistochemistry and immunocytofluorescence. TNF-alpha+ cells (< 10% of all cells) were found in all regions, predominantly in sublining and diffuse infiltrates. The highest percentage of TNF-R+ cells was found in the lining layer (50-90%), with a slight predominance of TNF-R55. In the sublining, fewer cells expressed TNF-R (approximately 50%), mostly TNF-R75. TNF-R75+ cells were also detectable in diffuse infiltrates and lymphoid aggregates (10-50%). These contained only individual TNF-R55+ cells. In diffuse infiltrates, there were slightly more TNF-R55+ cells than in lymphoid aggregates (in both cases < 10%). In sequential sections, TNF-alpha+ cells localized mostly in the vicinity of TNF-R+ cells. Macrophage-like cells appeared to be the predominant TNF-R+ cell type. CD3+ T cells in lymphoid aggregates expressed exclusively TNF-R75. Subsequently, the expression of membrane-bound TNF-alpha, TNF-R55 and TNF-R75 was tested by FACS analysis in isolated RA synoviocytes (n = 7 patients). Only four specimens expressed mTNF-alpha, and that on a low percentage of cells (2 +/- 2.4%; mean +/- SD). In contrast, all specimens expressed higher percentages of TNF-R55 and TNF-R75 (21 +/- 1% and 14 +/- 7.1%, respectively). These results demonstrate that: (1) the percentage of cells expressing soluble/transmembrane TNF-alpha is greatly outnumbered by the percentage of cells expressing TNF receptors; and (2) TNF-alpha-expressing cells are localized in regions expressing substantial levels of TNF receptors. Therefore, the known pro-inflammatory and pro-arthritic effects of TNF-alpha are probably mediated by local interactions between the receptors and their soluble and transmembrane ligands.
authors: Institute of Clinical Immunology and Rheumatology, Department of Medicine III, University of Erlangen-Nuremberg, Erlangen, Germany.
authors: S
authors: S
authors: Alsalameh
authors: K
authors: K
authors: Winter
authors: R
authors: R
authors: Al-Ward
authors: J
authors: J
authors: Wendler
authors: J R
authors: JR
authors: Kalden
authors: R W
authors: RW
authors: Kinne
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D002469:Cell Separation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012995:Solubility; D013583:Synovial Membrane / Q000276:immunology* / Q000473:pathology; D014018:Tissue Distribution; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D018836:Inflammation Mediators; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha