Substance P in Bronchial Asthma: Role in oxidant stress and in cell activation

Abstract

The substance P (SP) was described in the beginning of the XXth Century, and its biological actions was recognized to have implications in neurogenic inflammation and constriction of smooth muscles. The bronchial asthma prevalence has been increasing in all developed countries. The changes associated to inflammatory chronicity can compromise the organ function reversibility. The role of neuromechanisms in the pathology of the disease has been investigated considering the hypotheses that better therapeutic approaches can be achieved. The stimulation of human cells by SP leads to their activation and to reactive oxygen species (ROS) release. Consequently a persisting inflammatory disability is observed, mainly if a decrease in the anti-oxidant defence occurs. SP is a substrate for dipeptidyl peptidase IV (DPPIV), which is a multifunctional molecule with enzymatic and proinflammatory activities. CD26 was identified as the membrane DPPIV and is considered as an activation T cell marker, as well as CD25. The aim of the present study was therefore to analyse if serum SP values in long-term asthma patients, were associated to lung function parameters, considering the role of SP in neurogenic inflammation and in bronchoconstriction. It was also proposed to analyse the relationship of SP with superoxide dismutase (SOD) and total anti-oxidation activity in serum (TAS), considering the ROS production during the inflammatory process, as well as its association to CD26 and CD25 values and their immunologic and inflammatory properties. A group of individuals older than 65 years including 64 asthmatic patients (mean age 72.4±5.1 years) and 41 healthy individuals (mean age 79.2±7.0 years) was selected. Both subgroups were submitted to clinical observation, to skin prick tests and to SP, TAS and SOD. T cell CD26 and CD25 typing was also performed. Lung function tests were done to all patients. Among patients studied, 42 presented positive skin tests, mainly to house dust mites. Asthmatic patients presented significant increased values of SP (116.2±138.9 vs 39.5±17.9 pg/ml) when compared to controls and a significant decrease of TAS (.85±.13 vs .91±.10 mM) and SOD (588.1±156.l vs 822.9±179.5 U/gHb). All patients have clinical stability and presented forced expiratory volume in one second (FEV1) values of 73.6±25.3 l/s and peak expiratory flow (PEF50) of 38.8±26.7l. The CD25 expression was significantly increased in disease (14.3±5.9 vs 22.4±7.8) while CD26 was only slightly increased (41.9±10.2 vs 39.4±11.4). These results confirm the role of SP in the respiratory pathology studied and give a contribution for a better knowledge of the network of immunoinflammatory pathway, associated to this chronic disorder. A final goal for these studies would be a better diagnostic and therapeutic approach in this pathology