title: Alveolar macrophage depletion increases the severity of acute inflammation following nonlethal unilateral lung contusion in mice.
abstract: BACKGROUND
  Lung contusion (LC) is a common injury resulting from blunt thoracic trauma. LC is an important risk factor for the development acute lung injury, adult respiratory distress syndrome, and ventilator-associated pneumonia, all of which increase mortality from trauma. LC produces a nonspecific immune cellular response. Neutrophil recruitment is known to increase the severity of inflammation during LC. However, the exact role of macrophages in modulating the response to LC has not been well described.
  
  
  METHODS
  We used a cortical contusion impactor to induce unilateral LC in mice. Thoracic micro computed tomographic scans of these animals were obtained to document radiologic changes over time following LC. To understand the role of macrophages during LC, liposomal clodronate was used to deplete macrophage levels before traumatic insult. Acute inflammatory attributes after LC were assessed, by measuring pressure-volume mechanics; quantifying bronchial alveolar lavage levels of leukocytes, albumin, and cytokines; and finally examining lung specimen histopathology at 5, 24, 48, and 72 hours after injury.
  
  
  RESULTS
  After LC, alveolar macrophage numbers were significantly reduced and exhibited slowed recovery. Simultaneously, there was a significant increase in bronchial alveolar lavage neutrophil counts. The loss of macrophages could be attributed to both cellular apoptosis and necrosis. Pretreatment with clodronate increased the severity of lung inflammation as measured by worsened pulmonary compliance, increased lung permeability, amplification of neutrophil recruitment, and increases in early proinflammatory cytokine levels.
  
  
  CONCLUSIONS
  The presence of regulatory alveolar macrophages plays an important role in the pathogenesis of acute inflammation following LC.
authors.affiliation: From the Department of Surgery, University of Michigan, Ann Arbor, Michigan.
authors.forename: David
authors.initials: D
authors.lastname: Machado-Aranda
authors.forename: Madathilparambil
authors.initials: M
authors.lastname: V Suresh
authors.forename: Bi
authors.initials: B
authors.lastname: Yu
authors.forename: Vladislov
authors.initials: V
authors.lastname: Dolgachev
authors.forename: Mark R
authors.initials: MR
authors.lastname: Hemmila
authors.forename: Krishnan
authors.initials: K
authors.lastname: Raghavendran
mesh_terms: D000208:Acute Disease; D000818:Animals; D017209:Apoptosis; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D003288:Contusions / Q000276:immunology / Q000473:pathology*; D004195:Disease Models, Animal; D007111:Immunity, Cellular; D007249:Inflammation / Q000276:immunology / Q000473:pathology*; D055370:Lung Injury / Q000276:immunology / Q000473:pathology*; D016676:Macrophages, Alveolar / Q000276:immunology / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013898:Thoracic Injuries / Q000473:pathology; D014949:Wounds, Nonpenetrating / Q000276:immunology / Q000473:pathology*