Neuroimmune interactions: potential target for mitigating or treating intestinal radiation injury.
Intestinal radiation injury is characterized by breakdown of the epithelial barrier and mucosal inflammation. In addition to replicative and apoptotic cell death, radiation also induces changes in cellular function, as well as alterations secondary to tissue injury. The recognition of these "non-cytocidal" radiation effects has enhanced the understanding of normal tissue radiation toxicity, thus allowing an integrated systems biology-based approach to modulating radiation responses and providing a mechanistic rationale for interventions to mitigate or treat radiation injuries. The enteric nervous system regulates intestinal motility, blood flow and enterocyte function. The enteric nervous system also plays a central role in maintaining the physiological state of the intestinal mucosa and in coordinating inflammatory and fibroproliferative processes. The afferent component of the enteric nervous system, in addition to relaying sensory information, also exerts important effector functions and contributes critically to preserving mucosal integrity. Interactions between afferent nerves, mast cells as well as other cells of the resident mucosal immune system serve to maintain mucosal homeostasis and to ensure an appropriate response to injury. Notably, enteric sensory neurons regulate the activation threshold of mast cells by secreting substance P, calcitonin gene-related peptide and other neuropeptides, whereas mast cells signal to enteric nerves by the release of histamine, nerve growth factor and other mediators. This article reviews how enteric neurons interact with mast cells and other immune cells to regulate the intestinal radiation response and how these interactions may be modified to mitigate intestinal radiation toxicity. These data are not only applicable to radiation therapy, but also to intestinal injury in a radiological terrorism scenario.
Wang
J
J
Department of Surgery, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, AR 72205, USA.
Hauer-Jensen
M
M
D000818:Animals; D017615:Enteric Nervous System / Q000503:physiopathology* / Q000528:radiation effects; D006801:Humans; D007413:Intestinal Mucosa / Q000503:physiopathology / Q000528:radiation effects*; D008407:Mast Cells / Q000502:physiology / Q000528:radiation effects; D011832:Radiation Injuries / Q000276:immunology / Q000503:physiopathology* / Q000628:therapy; D015398:Signal Transduction