Lino dos Santos Franco Adriana, Domingos Helori Vanni, Damazo Amilcar Sabino, Breithaupt-Faloppa Ana Cristina, de Oliveira Ana Paula Ligeiro, Costa Soraia Kátia Pereira, Oliani Sonia Maria, Oliveira-Filho Ricardo Martins, Vargaftig B Boris, Tavares-de-Lima Wothan
Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Toxicology. 2009 Feb 27;256(3):157-63. doi: 10.1016/j.tox.2008.11.011. Epub 2008 Nov 21.
Clinical and experimental evidences show that formaldehyde (FA) exposure has an irritant effect on the upper airways. As being an indoor and outdoor pollutant, FA is known to be a causal factor of occupational asthma. This study aimed to investigate the repercussion of FA exposure on the course of a lung allergic process triggered by an antigen unrelated to FA. For this purpose, male Wistar rats were subjected to FA inhalation for 3 consecutive days (1%, 90-min daily), subsequently sensitized with ovalbumin (OVA)-alum via the intraperitoneal route, and 2 weeks later challenged with aerosolized OVA. The OVA challenge in rats after FA inhalation (FA/OVA group) evoked a low-intensity lung inflammation as indicated by the reduced enumerated number of inflammatory cells in bronchoalveolar lavage as compared to FA-untreated allergic rats (OVA/OVA group). Treatment with FA also reduced the number of bone marrow cells and blood leukocytes in sensitized animals challenged with OVA, which suggests that the effects of FA had not been only localized to the airways. As indicated by passive cutaneous anaphylactic reaction, FA treatment did not impair the anti-OVA IgE synthesis, but reduced the magnitude of OVA challenge-induced mast cell degranulation. Moreover, FA treatment was associated to a diminished lung expression of PECAM-1 (platelet-endothelial cell adhesion molecule 1) in lung endothelial cells after OVA challenge and an exacerbated release of nitrites by BAL-cultured cells. Keeping in mind that rats subjected solely to either FA or OVA challenge were able to significantly increase the cell influx into lung, our study shows that FA inhalation triggers long-lasting effects that affect multiple mediator systems associated to OVA-induced allergic lung such as the reduction of mast cells activation, PECAM-1 expression and exacerbation of NO generation, thereby contributing to the decrease of cell recruitment after the OVA challenge. In conclusion, repeated expositions to air-borne FA may impair the lung cell recruitment after an allergic stimulus, thereby leading to a non-responsive condition against inflammatory stimuli likely those where mast cells are involved.
临床和实验证据表明，接触甲醛（FA）会对上呼吸道产生刺激作用。作为一种室内和室外污染物，FA是职业性哮喘的一个致病因素。本研究旨在调查接触FA对由与FA无关的抗原引发的肺部过敏过程的影响。为此，雄性Wistar大鼠连续3天吸入FA（1%，每天90分钟），随后通过腹腔途径用卵清蛋白（OVA）-明矾致敏，2周后用雾化OVA进行激发。与未接触FA的过敏性大鼠（OVA/OVA组）相比，吸入FA后再进行OVA激发的大鼠（FA/OVA组）支气管肺泡灌洗中炎症细胞计数减少，表明OVA激发引起的肺部炎症强度较低。FA处理还减少了用OVA激发的致敏动物的骨髓细胞和血液白细胞数量，这表明FA的作用不仅局限于气道。如被动皮肤过敏反应所示，FA处理并未损害抗OVA IgE的合成，但降低了OVA激发诱导的肥大细胞脱颗粒程度。此外，FA处理与OVA激发后肺内皮细胞中血小板内皮细胞黏附分子1（PECAM-1）的肺表达减少以及BAL培养细胞中亚硝酸盐释放加剧有关。鉴于仅接受FA或OVA激发的大鼠能够显著增加肺内细胞流入，我们的研究表明，吸入FA会引发持久效应，影响与OVA诱导的过敏性肺相关的多个介质系统，如肥大细胞活化减少、PECAM-1表达降低和NO生成加剧，从而导致OVA激发后细胞募集减少。总之，反复接触空气中的FA可能会损害过敏刺激后肺细胞的募集，从而导致对可能涉及肥大细胞的炎症刺激无反应状态。
