Alveolar macrophage depletion increases the severity of acute inflammation following nonlethal unilateral lung contusion in mice.

Blunt thoracic trauma resulting in lung contusion (LC) is an important independent risk factor for the development of pneumonia, acute lung injury, and its more severe form known as adult respiratory distress syndrome. LC producing one of these respiratory complications results in mortality rates between 10% and 25% among adult trauma patients.1–3 Both macrophages and neutrophils are consistently recovered in bronchial alveolar lavage (BAL) fluid from patients with LC injury. While the importance of the neutrophils in the lung inflammatory response has been extensively studied, the role of alveolar macrophages (AMs) is a subject of debate.4,5 AMs are considered part of the nonspecific host immune system and have two main activation phenotypes as follows: M1 or classical phenotype mediates host defenses against bacteria, viruses, and protozoa. They are characterized by secreting a significant number of proinflammatory cytokines and have increased nitric oxide synthase activity resulting in the production of nitric oxide used for bacterial killing. Conversely, the M2 phenotype, also known as an alternative pathway, participates in helminth infections and probably has an important anti-inflammatory activity via interleukin 10 (IL-10) signaling. However, exuberant M2 activation along with their associated cytokine profile (IL-10, transforming growth factor β, and monocyte chemoattractant protein 1 [MCP-1]) has been implicated in persistent bacterial infection and pulmonary fibrosis.6–9 Previous experiments from our laboratory have shown that LC in mice significantly reduces the number of AMs present in BAL samples.10 Interestingly, we found that phagocytic capacity of AMs is improved and that polarization moves toward the M2 phenotype. Using CCR-2−/− mice, we found that some of these events are dependent on MCP-1 pathway. Thus, in this present study, to understand the precise role of AMs during LC, we performed experiments using macrophage-depleting agent clodronate before traumatic injury. Importantly, we found an increased severity of lung inflammation with diminution of AMs after LC injury.