title: Differential effects of female sex hormones on cellular recruitment and tracheal reactivity after formaldehyde exposure.
abstract: 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 naïve 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.
authors: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors: Adriana
authors: A
authors: Lino-dos-Santos-Franco
authors: Renata Midori
authors: RM
authors: Amemiya
authors: Ana Paula
authors: AP
authors: Ligeiro de Oliveira
authors: Ana Cristina
authors: AC
authors: Breithaupt-Faloppa
authors: Amílcar Sabino
authors: AS
authors: Damazo
authors: Ricardo Martins
authors: RM
authors: Oliveira-Filho
authors: Wothan
authors: W
authors: Tavares-de-Lima
mesh_terms: D000393:Air Pollutants / Q000633:toxicity; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000097:blood / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D005557:Formaldehyde / Q000633:toxicity*; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D009928:Organ Specificity; D010052:Ovariectomy; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011374:Progesterone / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014132:Trachea / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
chemical_list: D000393:Air Pollutants; D015815:Cell Adhesion Molecules; D005557:Formaldehyde; D011374:Progesterone; D004958:Estradiol; D003345:Corticosterone