Environmental Health Perspectives 105, Supplement 5, September 1997

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Localization of Intercellular Adhesion Molecule-1 (ICAM-1) in the Lungs of Silica-exposed Mice

Ricardo C. Nario and Andrea K. Hubbard

Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut

Abstract
Intercellular adhesion molecule-1 (ICAM-1) is expressed on a variety of cells including endothelial cells, alveolar epithelial cells, and alveolar macrophages. Endothelial/epithelial cell ICAM-1 participates in the migration of leukocytes out of the blood in response to pulmonary inflammation, whereas alveolar macrophage ICAM-1 may represent cell activation. Our previous studies have shown that there is increased expression of ICAM-1 in lung tissue during acute inflammation following intratracheal injection with silica particles (2 mg/mouse). This increased expression was shown to play a role, in part, in the migration of neutrophils from the circulation into the tissue parenchyma. The aim of the current work is to localize expression of ICAM-1 during acute inflammation in lungs of mice exposed to either silica or the nuisance dust, titanium dioxide. In silica-exposed mice, a significant increase in ICAM-1 was detected on day 1 and localized by immunohistochemistry to aggregates of pulmonary macrophages and to type II epithelial cells. Areas of the lung with increased ICAM-1 expression also showed increased tumor necrosis factor alpha expression. Immunocytochemical staining of bronchoalveolar lavage (BAL) cells demonstrated increased ICAM-1 expression associated with alveolar macrophages 3, 5, and 7 days following silica exposure. Finally, soluble ICAM-1 levels in the BAL fluid were significantly increased in mice exposed to silica on the same days. Titanium dioxide exposure elicited a minimal increase in expression of ICAM-1 in the lungs. These data demonstrate that exposure to the toxic particle silica specifically increases ICAM-1 expression localized to pulmonary macrophages and type II epithelial cells. -- Environ Health Perspect 105(Suppl 5):1183-1190 (1997)

Key words : ICAM-1, adhesion molecules, alveolar macrophages, pulmonary inflammation, silica, titanium dioxide

This paper is based on a presentation at The Sixth International Meeting on the Toxicology of Natural and Man-Made Fibrous and Non-Fibrous Particles held 15-18 September 1996 in Lake Placid, New York. Manuscript received at EHP 26 March 1997; accepted 2 April 1997.

This work was supported by grants from the University of Connecticut Research Foundation. R. Nario is supported by a fellowship from National Institutes of Health grant ES07163.

Address correspondence to Dr. A.K. Hubbard, Department of Pharmaceutical Sciences, School of Pharmacy, U-92, University of Connecticut, Storrs, CT 06269. Telephone: (860) 486-2084. Fax: (860) 486-4998. E-mail: hubbard@uconnvm.uconn.edu

Abbreviations used: AM, alveolar macrophage(s); BAL, bronchoalveolar lavage; ELISA, enzyme-linked immunosorbent assay; ICAM-1, intercellular adhesion molecule-1; IFN- gamma , interferon-gamma; IL-1, interleukin-1; PMN, neutrophil; PBS, phosphate buffered saline; sICAM-1, soluble intercellular adhesion molecule-1; TNF- alpha , tumor necrosis factor-alpha; TPBS, tween 20 in phosphate-buffered saline.

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Last Update: November 17, 1997