Advances in mast cell biology: new understanding of heterogeneity and function.

Mast cells are classically viewed as effector cells of IgE-mediated allergic diseases. However, over the last decade our understanding has been enriched about their roles in host defense, innate and adaptive immune responses, and in homeostatic responses, angiogenesis, wound healing, tissue remodeling, and immunoregulation. Despite impressive progress, there are large gaps in our understanding of their phenotypic heterogeneity, regulatory mechanisms involved, and functional significance. This review summarizes our knowledge of mast cells in innate and acquired immunity, allergic inflammation and tissue homeostasis, as well as some of the regulatory mechanisms that control mast cell development, phenotypic determination, and function, particularly in the context of mucosal surfaces.

Autonomic nervous system regulates secretion of anti-inflammatory prohormone SMR1 from rat salivary glands.

The autonomic nervous system regulates the secretion of bioactive proteins and peptides from salivary glands that can be important in systemic physiological responses. The prohormone submandibular rat-1, which is highly expressed in rat submandibular glands, can be cleaved to produce polypeptides with analgesic and anti-inflammatory activities. Human genes related to submandibular rat-1 have conserved biological functions and are potentially important in pain suppression, erectile function, and inflammation. In this study we describe the differential expression and posttranslational modification of submandibular rat-1 protein in salivary glands, the urogenital tract, lung, blood, and saliva in male Sprague-Dawley and Brown Norway rats. Submandibular rat-1 protein is secreted into saliva after the administration of beta-adrenergic or cholinergic agonists. Removal of the sympathetic ganglion that innervates the salivary glands results in increased levels of submandibular rat-1 protein in salivary glands. The secretion of submandibular rat-1 in response to physiological stress may provide a large pool of submandibular rat-1-derived peptide products that can promote analgesia and decrease inflammation locally and systemically. This pathway may be conserved among mammals and may constitute an important anti-inflammatory and analgesic response to stress.