Objective: Gouty arthritis is caused by precipitation in joints of crystals of monosodium urate (MSU). While it has been reported that mast cells (MCs) infiltrate gouty tophi, little is known about the actual roles of MCs during acute attacks of gout. This study was undertaken to assess the role of MCs in a mouse model of MSU crystal-induced acute arthritis. Methods: We assessed the effects of intra-articular (i.a) injection of MSU crystals in various strains of mice with constitutive or inducible MC deficiency, or in mice lacking IL-1β or other elements of innate immunity. We also assessed response to i.a. injection of MSU crystals in genetically MC-deficient mice after i.a. engraftment of wild-type or IL... More
Objective: Gouty arthritis is caused by precipitation in joints of crystals of monosodium urate (MSU). While it has been reported that mast cells (MCs) infiltrate gouty tophi, little is known about the actual roles of MCs during acute attacks of gout. This study was undertaken to assess the role of MCs in a mouse model of MSU crystal-induced acute arthritis. Methods: We assessed the effects of intra-articular (i.a) injection of MSU crystals in various strains of mice with constitutive or inducible MC deficiency, or in mice lacking IL-1β or other elements of innate immunity. We also assessed response to i.a. injection of MSU crystals in genetically MC-deficient mice after i.a. engraftment of wild-type or IL-β-/- bone marrow-derived cultured MCs. Results: We show that MCs can augment acute tissue swelling following i.a. injection of MSU crystals in mice. We report further that IL-1β production by MCs contributes importantly to MSU crystal-induced tissue swelling, particularly during its early stages, and that selective depletion of synovial MCs can diminish MSU crystal-induced acute inflammation in the joints. Conclusion: Our findings identify a previously unrecognized role for MCs and MC-derived IL-1β in contributing to the early stages of MSU crystal-induced acute arthritis in mice.
