Abstract. Acute lung injury (ALI) remains one of major causes of morbidity and mortality in intensive care medicine. The lack of efficient pharmacological interventions contributes to the high mortality rate of ALI. Losartan, an antagonist of angiotensin II (Ang II) type 1 receptor, is a potent therapeutic drug for ALI. Recent reports suggest that losartan inhibits the maturation of dendritic cells (DCs), impairs T-helper (Th) 1 immune response and ultimately attenuates inflammation in several Ang II-mediated inflammatory diseases. However, the possible protective mechanisms of losartan in ALI remain poorly understood. This study was aimed to define the effect of losartan on the frequency and phenotype of respiratory conventional DCs (cDCs) and Th cells polarization in lipopolysaccharide (LPS)-induced ALI mice. Results demonstrate that early after induction of LPS-induced ALI, cDCs expressing modest amounts of CD80 rapidly accumulated in the lungs. In addition, polarized Th1 and Th17 responses were markedly increased in LPS-induced ALI mice at 24 and 48 h. Of note, losartan led to inhibition of respiratory cDCs maturation at 6 h and suppressed Th1 and Th17 polarization responses compared with ALI mice at 24 and 48 h. Collectively, our findings may provide a novel and, at least, partial explanation for the protective effects by which losartan inhibits lung cDCs maturation and suppresses Th1 and Th17 immune responses.

Respiratory dendritic cells (DCs), especially conventional DCs (cDCs), are critically involved in the induction phase of the immune response in the respiratory system. However, little information concerning cDC kinetics in acute lung injury (ALI) is available. In this study, we have used a murine model of LPS-induced ALI to examine the kinetics and phenotype of respiratory, circulating and splenic cDCs. cDCs in the lung, blood, and spleen and the IL-6 level in the lung were detected at 6, 12 and 24 h after PBS or LPS challenge. In the ALI group, a rapid cDCs accumulation in the lung was observed, and there were highly significant correlations between the frequency of respiratory cDCs or the percentage of cDC expressing CD80 and the IL-6 concentration. However, the frequency of peripheral blood cDCs decreased rapidly in ALI mice, followed by a marked expansion. In addition, splenic cDCs only showed a transient expansion in ALI. cDCs within the blood, lungs and spleens had undergone a modest maturation in the ALI group. Our findings demonstrate that LPS-induced ALI provokes a dynamic and distinct distribution as well as phenotype changes in pulmonary, circulatory and splenic cDC populations. Lung cDCs may participate in the early inflammatory response to ALI.