EXPRESSION OF LUNG VASCULAR AND AIRWAY ICAM-1 AFTER EXPOSURE TO BACTERIAL LIPOPOLYSACCHARIDE

Airway instillation of bacterial lipopolysaccharide (LPS) into rat lun gs induces neutrophil accumulation, which is known to be intercellular adhesion molecule-1 (ICAM-1)-dependent. In the present study, ICAM-1 messenger RNA (mRNA) of whole lung was found to increase by 20-fold in this inflammatory model. This increase was reduced by 81% after treat ment of animals with anti-tumor necrosis factor-alpha (TNF-alpha) anti body and by 37% after treatment with anti-interleukin-1 (IL-1) antibod y. The same interventions reduced whole-lung ICAM-1 protein by 85% and 25%, respectively. The studies were extended to assess the locale in lung of ICAM-1, rose 4-fold after airway instillation of LPS. This ris e was also TNF-alpha-dependent. Under the same experimental conditions , fixation of [I-125]anti-ICAM-1 to airway surfaces increased 11-fold in a TNF-alpha-dependent manner. In situ hybridization and immunohisto chemical analyses of lung tissue revealed ICAM-1 upregulation in the b ronchiolar epithelium and in peribronchiolar smooth muscle. Soluble IC AM-1 could also be detected in bronchoalveolar lavage fluids (BALFs) o f animals after intratracheal instillation of LPS. Retrieved alveolar macrophages showed a small, significant, and transient increase in sur face expression of ICAM-1. These data indicate, at the very least, a d ual compartmentalized (vascular and airway) upregulation of ICAM-1 aft er airway instillation of LPS. This upregulation requires TNF-alpha an d IL-1. The functional significance of upregulated airway ICAM-1 remai ns to be determined.