The putative role of ovary removal and progesterone when considering the effect of formaldehyde exposure on lung inflammation induced by ovalbumin

OBJECTIVE: \ud \ud Formaldehyde exposure during the menstrual cycle is known to affect the course of allergic lung inflammation. Because our previous data demonstrated that formaldehyde combined with an ovariectomy reduced allergic lung inflammation, we investigated the putative role of ovary removal and progesterone treatment when considering the effect of formaldehyde on allergic lung inflammation.\ud \ud METHOD: \ud \ud Ovariectomized rats and their matched controls were exposed to formaldehyde (1%, 3 days, 90 min/day) or vehicle, and immediately after exposure, the rats were sensitized to ovalbumin by a subcutaneous route. After 1 week, the rats received a booster by the same route, and after an additional week, the rats were challenged with ovalbumin (1%) by an aerosol route. The leukocyte numbers, interleukin-10 (IL-10) release, myeloperoxidase activity, vascular permeability, ex vivo tracheal reactivity to methacholine and mast cell degranulation were determined 24 h later.\ud \ud RESULTS: \ud \ud Our results showed that previous exposure to formaldehyde in allergic rats decreased lung cell recruitment, tracheal reactivity, myeloperoxidase activity, vascular permeability and mast cell degranulation while increasing IL-10 levels. Ovariectomy only caused an additional reduction in tracheal reactivity without changing the other parameters studied. Progesterone treatment reversed the effects of formaldehyde exposure on ex vivo tracheal reactivity, cell influx into the lungs and mast cell degranulation.\ud \ud CONCLUSION: \ud \ud In conclusion, our study revealed that formaldehyde and ovariectomy downregulated allergic lung inflammation by IL-10 release and mast cell degranulation. Progesterone treatment increased eosinophil recruitment and mast cell degranulation, which in turn may be responsible for tracheal hyperreactivity and allergic lung inflammationFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP no.09/51886-3)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP no. 2011/51711-9)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP no. 2008/5108-3

Differential effects of female sex hormones on cellular recruitment and tracheal reactivity after formaldehyde exposure

Female sex hormones (FSHs) exert profound regulatory effects on the course of lung inflammation due to allergic and non-allergic immune responses. As pollution is one of the pivotal factors to induce lung dysfunction, in this study we investigated the modulatory role of FSHs on lung inflammation after a formaldehyde (FA) exposure. For this purpose, lung and systemic inflammatory responses were evaluated in terms of leukocytes countings in bronchoalveolar lavage (BAL), peripheral blood and bone marrow lavage from 7-day ovariectomized (OVx) and Sham-OVx rats subjected to FA inhalation for 3 consecutive days. The hypothesized link between effects of FSHs on expression of adhesion molecules and mast cells degranulation was also studied. Once exposed to FA, Sham-OVx rats increased the number of total cells recovered in BAL and of leukocytes in peripheral blood, and decreased the counts in bone marrow. By contrast, in OVx rats upon FA exposure there was a reduction of the total cells counts in BAL and of blood leukocytes: lung expressions of ICAM-1 and Mac-1 were depressed, but the number of bone marrow cells did not vary. Estradiol treatment of OVx rats increased the total cells in BAL and decreased the number of blood leukocytes, whereas the number of bone marrow cell remained unaltered. Progesterone treatment, in turn increased the total cells in BAL and blood leukocytes, but decreased the number of bone marrow cells. OVx rats exposed to FA developed tracheal hyperresponsiveness to methacholine (MCh). A similarly altered response was found between the tracheal segments of Sham-OVx rats after FA exposure and that found in tracheae of naive rats. Estradiol treatment prevented FA-induced tracheal hyperresponsiveness to MCh whereas progesterone was ineffective in this regard. In addition, OVx rats upon FA exposure significantly increased both, the ability of mast cell degranulation and serum corticosterone levels. In conclusion, it was found that FSHs act by distinct control mechanisms on FA-induced lung inflammation and tracheal hyperresponsiveness, since at low circulating levels of FSHs (such as those after OVx) there is some resistance to the development of a lung inflammatory response, but the cholinergic tracheal responsiveness is exacerbated. Our data also help to understand the involvement of FSHs on mast cells activity after pollutants exposure and add information regarding the role of FSHs on the mechanisms related to endothelium-leukocyte interactions. (C) 2011 Elsevier Ireland Ltd. All rights reserved.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[09/51886-3]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[08/50766-1]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[2008/58108-3]Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Conselho Nacional de Pesquisa (CNPq