Role of alveolar macrophages in acute lung injury model

Abstract

Alveolar macrophages (AM) play a key role in acute lung injury (ALI). Its depletion study would help us to evaluate the role of these cells in ALI and whether AM can be potential targets for the treatment of this syndrome. Aim: Evaluate the effect of AM in ALI model, through the depletion of these cells by the administration of clodronate liposomes. Sprague-Dawley rats (~300g) underwent intratracheal administration of HCl and Lipopolysaccharide (LPS)(30μg/g body weight) 2h later. Liposomes of PBS or clodronate (8µg/g body weight) were instilled 9h and 33h after HCl administration. Animals were sacrificed 72h after injury. AM depletion was determined by cell count and flow cytometry analysis. Body weight, lung weight and proteins in bronchoalveolar lavage (BAL) were assessed. Pro and anti-inflammatory mediators, markers of recruitment and apoptosis were analyzed in lung tissue and AM isolated from BAL. Data expressed as media±SEM, relative to GAPDH and fold over saline group (n=8 for all the study groups). One-Way-ANOVA and Newman Keuls post-hoc test were performed (p≤0.05). Clodronate liposomes reduced the percentage of AM to a 50% and did not produce any changes in body weight, lung weight, proteins levels or neutrophils infiltration. In the ALI model the expression of all the evaluated markers were increased. The depletion of AM in ALI model reduced IL1β and increased IL6 in lung tissue. Furthermore, the recruitment of de novo macrophages (CCL2) was reduced, and no changes were observed in neutrophils recruitment (CXCL1). Altogether indicate that AM have a major role in the ALI development and resolution. AM depletion in ALI model does not ameliorate lung injury, indicating that the presence of AM is essential to treat ALI.