| First Author | O'Brien AD | Year | 1999 |
| Journal | Am J Physiol | Volume | 276 |
| Issue | 6 Pt 1 | Pages | L961-70 |
| PubMed ID | 10362721 | Mgi Jnum | J:55939 |
| Mgi Id | MGI:1339804 | Doi | 10.1152/ajplung.1999.276.6.L961 |
| Citation | O'Brien AD, et al. (1999) Role of alveolar epithelial cell intercellular adhesion molecule-1 in host defense against Klebsiella pneumoniae. Am J Physiol 276(6 Pt 1):L961-70 |
| abstractText | Intercellular adhesion molecule-1 (ICAM-1) is expressed at high levels on type I alveolar epithelial cells (AEC) in the normal alveolar space. We postulate that AEC ICAM-1 enhances the antimicrobial activity of macrophages and neutrophils in the alveolar space. Wild-type and mutant mice deficient in ICAM-1 were inoculated intratracheally with Klebsiella pneumoniae. After 10 days, 43% of the ICAM- 1 mutant mice had died compared with 14% of the wild-type controls (P = 0.003). Significantly more bacteria were isolated from lungs of ICAM-1 mutant mice than controls 24 h after inoculation (log colony-forming units 5.14 +/- 0.21 vs. 3.46 +/- 0.16, P = 0.001). However, neutrophil recruitment to the lung was not different. In similar experiments in the rat, inhibition of alveolar ICAM-1 by intratracheal administration of antibody resulted in significantly impaired clearance of K. Pneumoniae. The role of phagocyte interactions with AEC ICAM-1 for antimicrobial activity was investigated in vitro using primary cultures of rat AEC that express abundant ICAM-1. Alveolar macrophage phagocytosis and killing of K. Pneumoniae were increased significantly in the presence of AEC; these effects were inhibited significantly (47.5 and 52%, respectively) when AEC ICAM-1 was blocked. Similarly, neutrophil phagocytic activity for K. Pneumoniae in the presence of AEC in vitro was decreased when ICAM-1 on the AEC surface was blocked. Thus in the absence of ICAM-1, there is impaired ability to clear K, pneumoniae from the lungs, resulting in increased mortality. These studies indicate that AEC ICAM-1 plays an important role in host defense against K. Pneumoniae by determining the antimicrobial activity of phagocytes within the lung. |
