Diminished ICAM-1 expression and impaired pulmonary clearance of nontypeable Haemophilus influenzae in a mouse model of chronic obstructive pulmonary disease/emphysema.

Abstract

The airways of patients with chronic obstructive pulmonary disease (COPD) are continually colonized with bacterial opportunists like nontypeable Haemophilus influenzae (NTHi), and a wealth of evidence indicates that changes in bacterial populations within the lung can influence the severity of COPD. In this study, we used a murine model for COPD/emphysema to test the hypothesis that COPD affects pulmonary clearance. Mice were treated with a pulmonary bolus of elastase, and as reported previously, the lungs of these mice were pathologically similar to those with COPD/emphysema at approximately 1 month posttreatment. Pulmonary clearance of NTHi was significantly impaired in elastase-treated versus mock-treated mice. While histopathologic analysis revealed minimal differences in localized lung inflammation between the two groups, lower levels of intercellular adhesion molecule 1 (ICAM-1) were observed for the airway epithelial surface of elastase-treated mice than for those of control mice. Following infection, elastase-treated mice had lung pathology consistent with pneumonia for as long as 72 h postinfection, whereas at the same time point, mock-treated mice had cleared NTHi and showed little apparent pathology. Large aggregates of bacteria were observed within damaged lung tissue of the elastase-treated mice, whereas sparse individual bacteria were observed in lungs of mock-treated mice at the same time point postinfection. Additional infection studies showed that NTHi mutants with biofilm defects were less persistent in the elastase-treated mice than the parent strain. These findings establish a model for COPD-related infections and support the hypotheses that ICAM-1 promotes clearance of NTHi. Furthermore, the data indicate that NTHi may form biofilms within the context of COPD-related infections.

• Authors: Bing Pang, Wenzhou Hong, Shayla L West-Barnette, Nancy D Kock, W Edward Swords
• Journal: Infection and immunity (Infect Immun) Vol. 76 Issue 11 Pg. 4959-67 (Nov 2008) ISSN: 1098-5522 [Electronic] United States
• PMID: 18794286 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Intercellular Adhesion Molecule-1

Topics

• Animals
• Biofilms
• Disease Models, Animal
• Haemophilus Infections (etiology)
• Haemophilus influenzae (immunology)
• Intercellular Adhesion Molecule-1 (biosynthesis)
• Mice
• Mucociliary Clearance (physiology)
• Pulmonary Emphysema (complications, microbiology, physiopathology)