title: Role of macrophage chemoattractant protein-1 in acute inflammation after lung contusion.
abstract: 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.
authors.affiliation: University of Michigan, Ann Arbor, MI 48109, USA. kraghave@umich.edu
authors.forename: Madathilparambil V
authors.initials: MV
authors.lastname: Suresh
authors.forename: Bi
authors.initials: B
authors.lastname: Yu
authors.forename: David
authors.initials: D
authors.lastname: Machado-Aranda
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Bender
authors.forename: Laura
authors.initials: L
authors.lastname: Ochoa-Frongia
authors.forename: Jadwiga D
authors.initials: JD
authors.lastname: Helinski
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Davidson
authors.forename: Paul R
authors.initials: PR
authors.lastname: Knight
authors.forename: Cory M
authors.initials: CM
authors.lastname: Hogaboam
authors.forename: Bethany B
authors.initials: BB
authors.lastname: Moore
authors.forename: Krishnan
authors.initials: K
authors.lastname: Raghavendran
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000502:physiology*; D003288:Contusions / Q000503:physiopathology*; D007249:Inflammation / Q000503:physiopathology*; D055370:Lung Injury / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010587:Phagocytosis; D051381:Rats; D020318:Rats, Long-Evans
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2