Expression of Lung Vascular and Airway ICAM-1 after Exposure to Bacterial Lipopolysaccharide

Abstract

Airway instillation of bacterial lipopolysaccharide (LPS) into rat lungs 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 treatment of animals with anti-tumor necrosis factor-alpha (TNF-alpha) antibody and by 37% after treatment with anti-interleukin-1 (IL-1) antibody. 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-I upregulation. Lung vascular ICAM-1 content, which was assessed by vascular fixation of [125I]anti-ICAM-1, rose 4-fold after airway instillation of LPS. This rise was also TNF-alpha-dependent. Under the same experimental conditions, fixation of [125I]anti-ICAM-1 to airway surfaces increased 11-fold in a TNF-alpha-dependent manner. In situ hybridization and immunohistochemical analyses of lung tissue revealed ICAM-1 upregulation in the bronchiolar epithelium and in peribronchiolar smooth muscle. Soluble ICAM-1 could also be detected in bronchoalveolar lavage fluids (BALFs) of animals after intratracheal instillation of LPS. Retrieved alveolar macrophages showed a small, significant, and transient increase in surface expression of ICAM-1. These data indicate, at the very least, a dual compartmentalized (vascular and airway) upregulation of ICAM-1 after airway instillation of LPS. This upregulation requires TNF-alpha and IL-1. The functional significance of upregulated airway ICAM-1 remains to be determined.

Differential Effects of Ebselen on Neutrophil Recruitment, Chemokine, and Inflammatory Mediator Expression in a Rat Model of Lipopolysaccharide-Induced Pulmonary Inflammation

“…ICAM-1 has previously been shown to be a requirement for neutrophil recruitment after airway instillation of LPS with peak levels of expression associated with maximum leukocyte adherence (35). In agreement with published data, we found that lung ICAM-1 expression was up-regulated by LPS exposure (24,25). Ebselen dose-dependently abrogated ICAM-1 mRNA expression.…”

“…These data suggest that the inhibitory effect of ebselen on LPS-induced neutrophil influx and ICAM-1 expression is partially achieved through an inhibitory effect on IL-1␤. In agreement with an important role of IL-1␤ in this model are the findings showing that an anti-IL-1 Ab reduced LPS-induced lung ICAM-1 mRNA expression, which is necessary for neutrophil recruitment (25).…”

“…IL-1␤ together with TNF-␣ are potent inducers of ICAM-1 expression which has previously been shown to be a requirement for neutrophil recruitment after airway instillation of LPS (24,25,35). Therefore, we postulated that the beneficial effect of ebselen might occur through the ability of this agent to prevent lung ICAM-1 expression.…”

“…Expression of CD18 adhesion molecules on the PMN surface can be induced by exposure to LPS or TNF-␣ and to chemokines such as CINC-1 and MIP-2 (20 -23). In rats, treatment with Abs to CD11a/CD18 or CD11b/ CD18, as well as to their ICAM-1 endothelial cell ligand, attenuated the migration of PMNs to intrapulmonary LPS (24,25).…”

Response toNeisseria gonorrhoeaeby Cervicovaginal Epithelial Cells Occurs in the Absence of Toll-Like Receptor 4-Mediated Signaling

“…Perhaps most confusing are the data on gastrointestinal epithelial cells, where the ability of LPS to up-regulate proinflammatory cytokines appears to vary with the cell line tested (67)(68)(69)(70). In addition, airway epithelial cells have demonstrated sensitivity to LPS by NF-B activation, cytokine production, and up-regulation of various defense molecules (71)(72)(73)(74), and LPS has been shown to simulated cytokine expression by human gingival epithelial cells (75)(76)(77). None of these studies identified host cell surface moieties linked to epithelial-LPS interactions.…”