Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/17966
Title: Role of the Neuropeptide Substance P in Burn-Induced Distant Organ Damage
Authors: SELENA SIO WEISHAN
Keywords: Burn, Lung, Substance P, Neutrophil, Cytokines, Neuropeptide
Issue Date: 3-Dec-2009
Source: SELENA SIO WEISHAN (2009-12-03). Role of the Neuropeptide Substance P in Burn-Induced Distant Organ Damage. ScholarBank@NUS Repository.
Abstract: The classical tachykinin substance P (SP) has numerous potent neuroimmunomodulatory effects in many inflammatory diseases. Belonging to a class of neuro-mediators targeting not only residential cells but also inflammatory cells, studying SP provides important information on the bidirectional linkage between how neural function affects inflammatory events and in turn, how inflammatory responses alter neural activity. Burn injuries are one of the most common and devastating forms of trauma. One of the major causes of mortality in burn patients is respiratory failure, due to the development of acute lung injury (ALI), even without direct inhalational injury. Hence, much research interest is focused on understanding the role of mediators that contribute to the pathophysiology of burn-induced ALI. However, the role of SP in inducing inflammation in the lungs after burn injury is not known. Therefore, this study aimed to investigate whether SP instigates distant pulmonary SP release and ALI after severe local burn injury. A 30% total body surface area full-thickness burn induced in male Balb/c wild-type (WT) mice showed heightened pulmonary SP production and SP-neurokinin-1-receptor (NK1R) signaling, a G protein coupled receptor, which SP binds preferentially to. Concurrently, elevated pro-inflammatory cytokines, chemokines, neutrophil infiltration, and increased microvascular permeability were observed. Furthermore, histological examination reveals higher alveolar congestion, interstitial inflammatory cellular infiltrates and edema, all of which are evidences of severe ALI. Notably, these effects were abolished in burn-injured WT mice pre-treated with L703606, a specific NK1R antagonist, and in burn-injured preprotachykinin-A (PPT-A) gene deficient mice, which encodes for SP; while exogenous administration of SP to burn-injured PPT-A-/- mice restored the inflammatory response and ALI. Results of the present study provide for the first time compelling evidence, that the enhanced release of SP levels in lung and blood could be a critical factor leading to the pathophysiology of remote ALI and disruption of breathing function early after severe local burn injury. Taken together, with an in-depth understanding of the early pro-inflammatory effects of SP, new approaches maybe achieved for the prevention of an acute inflammatory cascade and treatment of ALI in critically injured patients.
URI: http://scholarbank.nus.edu.sg/handle/10635/17966
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