Role of macrophage chemoattractant protein-1 in acute inflammation after lung contusion

MV Suresh, B Yu, D Machado-Aranda… - American Journal of …, 2012 - atsjournals.org
MV Suresh, B Yu, D Machado-Aranda, MD Bender, L Ochoa-Frongia, JD Helinski…
American Journal of Respiratory Cell and Molecular Biology, 2012atsjournals.org
Lung contusion (LC), commonly observed in patients with thoracic trauma is a leading risk
factor for development of acute lung injury/acute respiratory distress syndrome. Previously,
we have shown that CC chemokine ligand (CCL)-2, a monotactic chemokine abundant in
the lungs, is significantly elevated in LC. This study investigated the nature of protection
afforded by CCL-2 in acute lung injury/acute respiratory distress syndrome during LC, using
rats and CC chemokine receptor (CCR) 2 knockout (CCR2−/−) mice. Rats injected with a …
Lung contusion (LC), commonly observed in patients with thoracic trauma is a leading risk factor for development of acute lung injury/acute respiratory distress syndrome. Previously, we have shown that CC chemokine ligand (CCL)-2, a monotactic chemokine abundant in the lungs, is significantly elevated in LC. This study investigated the nature of protection afforded by CCL-2 in acute lung injury/acute respiratory distress syndrome during LC, using rats and CC chemokine receptor (CCR) 2 knockout (CCR2−/−) mice. Rats injected with a polyclonal antibody to CCL-2 showed higher levels of albumin and IL-6 in the bronchoalveolar lavage and myeloperoxidase in the lung tissue after LC. Closed-chest bilateral LC demonstrated CCL-2 localization in alveolar macrophages (AMs) and epithelial cells. Subsequent experiments performed using a murine model of LC showed that the extent of injury, assessed by pulmonary compliance and albumin levels in the bronchoalveolar lavage, was higher in the CCR2−/− mice when compared with the wild-type (WT) mice. We also found increased release of IL-1β, IL-6, macrophage inflammatory protein-1, and keratinocyte chemoattractant, lower recruitment of AMs, and higher neutrophil infiltration and phagocytic activity in CCR2−/− mice at 24 hours. However, impaired phagocytic activity was observed at 48 hours compared with the WT. Production of CCL-2 and macrophage chemoattractant protein-5 was increased in the absence of CCR2, thus suggesting a negative feedback mechanism of regulation. Isolated AMs in the CCR2−/− mice showed a predominant M1 phenotype compared with the predominant M2 phenotype in WT mice. Taken together, the above results show that CCL-2 is functionally important in the down-modulation of injury and inflammation in LC.
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