Low-dose carbon monoxide treatment attenuates early pulmonary neutrophil recruitment after acid aspiration

• Published in: American journal of physiology. Lung cellular and molecular physiology 2008-04, Vol.294 (4), p.L644-L653
• Main Authors: Nemzek, Jean A, Fry, Christopher, Abatan, Omorodola
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - therapeutic use; Carbon monoxide; Carbon Monoxide - therapeutic use; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Flow Cytometry; Humans; Inflammation - drug therapy; Inflammation - pathology; Leukocyte Count; Lung - pathology; Lungs; Mice; Mice, Inbred ICR; Neutrophils - drug effects; Neutrophils - physiology; Organ Size; Pneumonia, Aspiration - drug therapy; Pneumonia, Aspiration - pathology; Respiratory diseases; Respiratory therapy; Rodents
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00324.2007

1 Unit for Laboratory Animal Medicine and 2 Department of Pathology, University of Michigan, Ann Arbor, Michigan Submitted 14 August 2007 ; accepted in final form 11 January 2008 Exogenous carbon monoxide (CO) has anti-inflammatory and cytoprotective properties that show promise in the treatment of numerous pulmonary diseases. However, the effectiveness of CO in acute pulmonary injury associated with direct lung insult has not been shown conclusively. The purpose of this study was to determine if exogenous CO would modulate the pulmonary inflammation and lung injury that develops after acid aspiration. Groups of mice were given intratracheal (IT) injections of either saline or an acidic solution. After the IT injection, some of the mice in each group were allowed to spontaneously inhale CO (500 ppm). Mice exposed to CO for 6 h after IT acid had a significant decrease in bronchoalveolar lavage (BAL) fluid neutrophil counts and in histological evidence of lung injury. These results could not be explained by changes in BAL fluid chemokine levels or altered CXCR2 expression. The reduced neutrophil recruitment was associated with a decrease in the percentage of peripheral blood neutrophils expressing CD11b protein. However, within 24 h, the BAL neutrophil counts increased and were not different from animals without CO exposure. In addition, indices of vascular integrity were not different between animals with acid aspiration regardless of CO exposure at the later time point. These results showed that CO can modulate the early development of acute lung inflammation in this model of acid aspiration. Although these effects were eventually overwhelmed, the results suggest that CO may have efficacy during the initial treatment of aspiration lung injury. lung injury; chemokines; CXCR2; CD11b; inflammation Address for reprint requests and other correspondence: J. A. Nemzek, Univ. of Michigan, Unit for Laboratory Animal Medicine and Dept. of Pathology, 018 ARF, 1150 W. Medical Center Drive, Ann Arbor, MI 48109 (e-mail: jnemzek{at}umich.edu )