• Nicolás Mangado, Sandra Pérez-Rial, Raúl Terrón-Expósito, and Alvaro Girón-Martínez.
• Chest. 2014 Mar 1;145(3 Suppl):615A.

Session TitleTobacco Cessation and Prevention PostersSESSION TYPE: Poster PresentationsPRESENTED ON: Saturday, March 22, 2014 at 01:15 PM - 02:15 PMPURPOSE: This study investigates the role of proinflammatory monocytes recruited from blood and recovered in bronchoalveolar lavage (BAL) fluid in mediating the lung damage in a model of acute cigarette smoke (CS)-induced lung inflammation in two strains of mice with different susceptibility to develop emphysema.MethodsStrains of mice susceptible-C57BL/6J and non susceptible-129S2/SvHsd were exposure to whole-body CS for 3 consecutive research cigarettes in one single day in order to induce acute inflammation in the lung. BAL fluid was analyzed by flow cytometry to evaluate the influx of leukocyte population and MMP-12, TNF-α and NF-KB were studied in the lung tissue. To determine the functional role of these proinflammatory monocytes in mediating CS-induced airway inflammation, alveolar macrophages and blood monocytes were transiently removed by pretreatment with liposome-encapsulated CL2MDP, given 2 and 4 days prior to CS exposure and their repopulation was studied.ResultsAnalysis of BAL fluid showed more influx of recently migrated monocytes at 72h after CS-exposition in susceptible compared to non susceptible mice. It correlated with an increase in MMP-12 and TNF-α protein levels and with an increment of NF-KB translocation to the nucleus in C57BL/6J mice. 48h after CL2MDP treatment, monocytes/macrophages were maximally depleted and subsequently recently migrated monocytes reappeared in BAL fluid of susceptible mice at 72h after CS exposure. Recently migrated monocytes influx to the lung correlated with an increase in the MMP-12 protein level, indicating that the increase in proinflammatory monocytes is associated with a major tissue damaging.ConclusionsOur data confirm that the recruitment of proinflammatory recently migrated monocytes from the blood are responsible for the increase in MMP-12 and has an important role in the pathogenesis of lung disease induced by acute lung inflammation. These results could contribute to understanding the different susceptibility to CS of these strains of mice.Clinical ImplicationsEarly diagnosis is of key importance in the treatment of emphysema. The response pattern we observed suggests that acute CS exposure may be useful to understand pathogenic mechanisms triggered by CS in the lungs including inflammation and alteration of host defiance. Importantly, the response of immunologic system precedes the onset of susceptibility to develop emphysema and thus, in order to develop effective therapeutic drugs it is critical to focus on these early events.DisclosureThe following authors have nothing to disclose: Sandra Pérez-Rial, Raúl Terrón-Expósito, Álvaro Girón-Martínez, Nicolás Mangado, Germán Peces-BarbaNo Product/Research Disclosure Information.

20 keywords...

hide…