Mast cells, cytokines, and metalloproteinases at the rheumatoid lesion: dual immunolocalisation studies.
OBJECTIVE
To examine the distribution and activation of mast cells (MCs) in the rheumatoid lesion (cartilage-pannus junctions demonstrating cartilage erosion), and to determine whether or not their tissue distribution is related to that for tumour necrosis factor alpha (TNF alpha), interleukin-1 (IL-1), stromelysin-1, and collagenase.


METHODS
Immunolocalisation of MC-tryptase was used to identify MCs and their states of degranulation in 35 specimens of cartilage-pannus junctions. Dual immunolocalisation techniques using alkaline phosphatase and peroxidase conjugated antibodies were used to compare the distributions of MCs with the proinflammatory cytokines TNF alpha and IL-1, and the cartilage or matrix degrading enzymes stromelysin-1 and collagenase.


RESULTS
Stromelysin-1, TNF alpha, and IL-1 beta were especially prominent at the cartilage-pannus junctions, albeit with patchy distributions. Extracellular MC tryptase, indicative of MC activation/degranulation, was commonly observed at sites of cartilage erosion, and was often associated with the microenvironmental expression of TNF alpha, IL-1 beta, stromelysin-1, and collagenase. Such observations were often associated with localised sites of tissue oedema and stromal disruption.


CONCLUSIONS
MC activation was frequently associated with proinflammatory cytokine and metalloproteinase expression by neighbouring cells, thereby suggesting an important contributory role for the MC in mediating matrix degradation and oedematous changes within microfoci of the rheumatoid lesion.
D000368:Aged; D001172:Arthritis, Rheumatoid / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D053818:Chymases; D017364:Collagenases / Q000032:analysis; D016207:Cytokines / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000032:analysis; D008297:Male; D008407:Mast Cells / Q000201:enzymology / Q000473:pathology*; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000032:analysis*; D008875:Middle Aged; D012697:Serine Endopeptidases / Q000032:analysis*; D053802:Tryptases; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D016207:Cytokines; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; D053802:Tryptases; D017364:Collagenases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3