[Hypereosinophilic syndrome accompanied with digital gangrene: efficacy of therapeutic angiogenesis by autologous bone marrow mononuclear cells transplantaion].

A 62-year-old-man presented to our hospital with complaints of coldness, numbness, pain, weakness and cyanosis on the fingers and toes in March 2010. Laboratory findings revealed marked eosinophilia (46.6%; WBC 20600/µl), an elevation of serum creatine kinase, proteinuria and hematuria. He was diagnosed as hypereosinophilic syndrome (HES) without evidence to support a diagnosis of underlying diseases causing eosinophilia. After the initiation of corticosteroid therapy, peripheral eosinophil count was dramatically decreased, and both serum CK value and urinary findings became normalized. However, his symptoms persisted and digital necrotic changes developed. Angiography of the bilateral upper and lower extremities showed multiple arterial occlusions with poor collaterals. The digital gangrenes were unresponsive to peripheral circulation ameliorators and gradually progressed. In July 2010, autologous transplantation of bone marrow mononuclear cells was performed for achievement of therapeutic angiogenesis. His digital skin color was ameliorated by the angiogenic therapy in two weeks, and digital gangrenes did not progress after that. After amputation of his fingers and toe, cut surfaces healed with favorable epithelization, and the symptoms were subsequently eliminated. Moreover, during three years after the therapy, as well as the effect on the skin lesion, the significant improvement in peripheral circulation was observed. Therefore, we proposed that therapeutic angiogenesis by autologous bone marrow mononuclear cells transplantation was a novel and effective treatment for intractable digital gangrene associated with HES.

Immunoglobulin E-independent activation of mast cell is mediated by Mrg receptors.

Mast cells play a central role in inflammatory and allergic reactions by releasing inflammatory mediators through two main pathways, immunoglobulin E-dependent and -independent activation. In the latter, mast cells are activated by a diverse range of basic molecules, including peptides and amines such as substance P, neuropeptide Y, and compound 48/80. These secretagogues are thought to activate the G proteins in mast cells through a receptor-independent mechanism. Here, we report that the basic molecules activate G proteins through the Mas-related gene (Mrg) receptors on mast cells, leading to mast cell degranulation. We suggest that one of the Mrg receptors, MrgX2, has an important role in regulating inflammatory responses to non-immunological activation of human mast cells.