Mast cell responses in rheumatoid synovium. Association of the MC_TC subset with matrix turnover and clinical progression

Abstract

Objective. To determine the distribution of mast cell subsets and their density in synovium from normal subjects and from patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Methods. A sequential double‐immunohisto‐chemical staining technique was used to distinguish mast cells as positive for tryptase only (MCT) or for tryptase plus chymase (MCTC). Synovial tissue was obtained from RA patients (n = 16), OA patients (n = 18), and normal subjects (n = 15). Sections were analyzed to a depth of 1 mm from the synoviocyte lining layer by quantitative histomorphometry. Immunohisto‐chemical data were correlated with histologic findings and clinical indices of disease activity. Results. In normal synovium, the majority of mast cells belonged to the MCTC subset, outnumbering MCT cells by 5:1. The mean density of mast cells was significantly increased in RA synovia (60.9 cells/mm2) compared with OA (21.7 cells/mm2) and with normal (9.4 cells/mm2) synovia. Selective expansion of the MCT subset accounted for the increased mast cell density in OA. In RA, both subsets expanded and were associated with infiltrating inflammatory cells or with regions of highly cellular fibrous tissue (mainly MCTC). An association was noted between clinical parameters of activity or progression of rheumatoid disease and the density of MCTC cells, especially the density in the superficial layer of synovium. In RA synovia, we found no evidence of the chymase only, or MCC, immunophenotype. Conclusion. MCTC mast cells expand in RA but not OA, associate with regions of “active” fibrosis, and correlate with parameters of disease activity or progression of RA. These findings implicate the MCTC subset of mast cells in the pathologic mechanisms that mediate tissue damage in RA.

Emerging roles of serine proteinases in tissue turnover in arthritis

“…70). Tryptase and chymase are the major serine proteinases stored and secreted by mast cells and are present in synovium and the cartilagepannus junction in arthritis (71,72). Both enzymes promote inflammation, ECM destruction, and remodeling by several mechanisms (for review, see ref.…”

Human Mast Cell-Derived Gelatinase B (Matrix Metalloproteinase-9) Is Regulated by Inflammatory Cytokines: Role in Cell Migration

“…Mast cells can also undergo significant change in number or in phenotype during allergic or nonallergic inflammation (1,(5)(6)(7)(8)(9). These cells play a crucial role in IgE-dependent immune responses that mediate immediate hypersensitivity reactions associated with allergic phenomena and host resistance to parasites (5,10).…”

“…These include the production of inflammatory (13,14) and tissue destructive (15,16) mediators. Moreover, a significant increase in mast cell numbers has been documented in human synovial tissue derived from patients with RA (8,9). Despite the extensive knowledge regarding the mediators that regulate mast cell phenotype and number (10), factors that regulate the homing of mast cell progenitors from the bone marrow to the tissue of residence are not well-defined.…”

IL-15 induces mast cell migration via a pertussis toxin-sensitive receptor

“…Increased expression of these factors during an inflammatory response may induce accumulation of mast cells. Increased mast cell numbers are characteristic of many inflammatory disorders including asthma [15], rheumatoid arthritis [16][17][18][19][20] and inflammatory bowel disease [21][22][23]. Interestingly, recent reports suggest that both IL-15 expression [17,[24][25][26] and mast cell density are increased in rheumatoid synovium [17,18].…”