Pulmonary neutrophil recruitment and bronchial reactivity in formaldehyde-exposed rats are modulated by mast cells and differentially by neuropeptides and nitric oxide.
We have used a pharmacological approach to study the mechanisms underlying the rat lung injury and the airway reactivity changes induced by inhalation of formaldehyde (FA) (1% formalin solution, 90 min once a day, 4 days). The reactivity of isolated tracheae and intrapulmonary bronchi were assessed in dose-response curves to methacholine (MCh). Local and systemic inflammatory phenomena were evaluated in terms of leukocyte countings in bronchoalveolar lavage (BAL) fluid, blood, bone marrow lavage and spleen. Whereas the tracheal reactivity to MCh did not change, a significant bronchial hyporesponsiveness (BHR) was found after FA inhalation as compared with naive rats. Also, FA exposure significantly increased the total cell numbers in BAL, in peripheral blood and in the spleen, but did not modify the counts in bone marrow. Capsaicin hindered the increase of leukocyte number recovered in BAL fluid after FA exposure. Both compound 48/80 and indomethacin were able to prevent the lung neutrophil influx after FA, but indomethacin had no effect on that of mononuclear cells. Following FA inhalation, the treatment with sodium cromoglycate (SCG), but not with the nitric oxide (NO) synthase inhibitor L-NAME, significantly reduced the total cell number in BAL. Compound 48/80, L-NAME and SCG significantly prevented BHR to MCh after FA inhalation, whereas capsaicin was inactive in this regard. On the other hand, indomethacin exacerbated BHR. These data suggest that after FA inhalation, the resulting lung leukocyte influx and BHR may involve nitric oxide, airway sensory fibers and mast cell-derived mediators. The effect of NO seemed to be largely restricted to the bronchial tonus, whereas neuropeptides appeared to be linked to the inflammatory response, therefore indicating that the mechanisms responsible for the changes of airway responsiveness caused by FA may be separate from those underlying its inflammatory lung effects.
Lino dos Santos Franco
Adriana
A
Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Damazo
Amílcar Sabino
AS
Beraldo de Souza
Hyula Regines
HR
Domingos
Helory Vanni
HV
Oliveira-Filho
Ricardo Martins
RM
Oliani
Sonia Maria
SM
Costa
Soraia Katia Pereira
SK
Tavares de Lima
Wothan
W
D000393:Air Pollutants / Q000633:toxicity; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000378:metabolism / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde / Q000633:toxicity*; D066298:In Vitro Techniques; D008168:Lung / Q000473:pathology*; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D016210:Methacholine Chloride / Q000494:pharmacology; D009479:Neuropeptides / Q000502:physiology*; D009504:Neutrophils / Q000187:drug effects* / Q000473:pathology; D009569:Nitric Oxide / Q000502:physiology*; D011014:Pneumonia / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014132:Trachea / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology
D000393:Air Pollutants; D000893:Anti-Inflammatory Agents; D009479:Neuropeptides; D016210:Methacholine Chloride; D005557:Formaldehyde; D009569:Nitric Oxide