Abstract
BACKGROUND: Mast cells (MC) are ubiquitous resident cells, traditionally viewed as effector cells of allergic reactions that can store and synthesize de novo many mediators upon activation by a variety of stimuli. Exciting new insights are unveiling MC involvement in the pathogenesis of connective tissue disorders including wound healing and fibrosis. THE PROBLEM: Abnormal wound repair is associated with an increased number of MC strategically located around blood vessels. Therapeutic local manipulation of MC population and reactivity may help improve and even prevent impaired repair processes for which there is no cure. BASIC/CLINICAL SCIENCE ADVANCES: Chymase, a MC-restricted protease, is pre-stored in MC cytoplasmic granules with other mediators. The development of a highly specific inhibitor targeting chymase established its pivotal effect on fibrosis pathogenesis in a mouse model of silica-induced fibrosis. This novel finding evokes the potential therapeutic relevance of chymase inhibition to prevent aberrant wound healing. CLINICAL CARE RELEVANCE: MC are increased in number in a variety of fibrotic diseases, compared to normal scars. Chymase has become a rising target prompting the development of chymase-specific inhibitors to be used as prophylactic or therapeutic agents. Another emerging strategy may consist in evaluating the efficacy of mast cell stabilizing drugs such as cromolyn in abnormal wound healing-drugs which are already approved for human use in other MC-driven disorders. CONCLUSION: Limited treatment success of dysregulated wound healing underscores the need for novel targets be considered such as MC and/or MC-derived mediators and the necessity to design new therapeutic strategies for wounds that remain difficult to treat.