Mast Cells May Initiate Sequence of Events Leading to Inflammatory...

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Mast Cells May Initiate Sequence of Events Leading to Inflammatory Arthritis

By Karla Gale

NEW YORK (Reuters Health) Sept 05 - Synovial mast cells appear to clear the

way for the joint destruction common to inflammatory forms of arthritis,

scientists at Harvard Medical School report in the September 6th issue of

Science.

Although much is known about the role of autoantibodies, complement and

cytokines in causing synovial destruction, the pathways leading to their

initial activity remain unexplained, Dr. M. Lee and his Boston-based

investigative team note.

When wild-type mice were injected with arthritogenic serum from an

engineered mouse model of erosive arthritis, synovial hyperplasia, pannus

formation and inflammatory infiltrates resulted. In contrast, mast

cell-deficient mice demonstrated almost no evidence of clinical joint

inflammation or histopathology after such treatment.

When the researchers transferred bone marrow mast cells from wild-type mice

into the mast-cell deficient mice and allowed time for engraftment, the

arthritogenic serum did cause joint erosions, the authors note. In addition,

the mast cells rapidly degranulated within the first hours after serum

transfer, prior to the overt onset of inflammation.

" It is likely that synovial mast cells are activated by articular

autoantibody immune complexes suggestive of an immune complex

hypersensitivity (Arthus) reaction in the synovium, " the group writes.

The researchers theorize that mast cells may play a role in human arthritis

conditions associated with the formation of immune complexes, such as

rheumatoid arthritis, cryoglobulin-associated synovitis in hepatitis C

infection and postinfectious arthritis.

" We are very interested in finding out what specifically is activating mast

cells and in further defining their role in arthritis, " Dr. Lee said in an

interview with Reuters Health.

But because his team's research was carried out in a mouse model of

inflammatory arthritis, it is not yet possible to " draw a direct line to

human arthritic conditions, " he noted.

Science 2002;297:1689-1692.