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Smoke and C5a Induce Airway Epithelial Intercellular Adhesion Molecule-1 and Cell Adhesion

Division of Pulmonary and Critical Care Medicine, School of Allied Health Professions, and Department of Preventive and Societal Medicine, University of Nebraska Medical Center, Omaha, Nebraska; and Brown University, Providence, Rhode Island

Address correspondence to: Anthony A. Floreani, Division of Pulmonary and Critical Care Medicine, 985300 University of Nebraska Medical Center/Nebraska Health Systems, Omaha, NE 68198-5300. E-mail: aflorean{at}unmc.edu

The human bronchial epithelial cell is one of the first cell types to be exposed to the irritants and toxins present in inhaled cigarette smoke. The ability of the bronchial epithelium to modulate inflammatory and immune events in response to cigarette smoke is important in the pathogenesis of smoke-induced airway injury. We have shown that cigarette smoke extract and the complement anaphylatoxin C5a both independently induce increased expression of intercellular adhesion molecule (ICAM)-1 on airway epithelial monolayers compared with unstimulated cells in vitro. This enhanced ICAM-1 expression is associated with a greater capacity of the airway epithelial cells to bind mononuclear cells, a process that appears to require the proinflammatory cytokine tumor necrosis factor- and protein kinase C intracellular signaling. Exposure of epithelial monolayers to the combination of cigarette smoke followed by C5a results in an additive response for ICAM-1 expression and mononuclear cell adhesion compared with smoke or C5a challenge alone. Inhibiting C5a receptor expression can attenuate these responses. These findings suggest that smoke exposure in some way enhances the functional responsiveness of the C5a receptor expressed on these airway epithelial cells for subsequent C5a-mediated increases in ICAM-1 expression and mononuclear cell adhesion. Our results may help explain the initiation and propagation of inflammatory events in vivo induced by chronic airway exposure to cigarette smoke.

Abbreviations: antibody, ab • bronchoalveolar lavage, BAL • bovine serum albumin, BSA • chronic obstructive pulmonary disease, COPD • cigarette smoke extract, CSE • human bronchial epithelial cell, HBEC • intercellular adhesion molecule-1, ICAM-1 • interleukin, IL • leukocyte function–associated antigen-1, LFA-1 • peripheral blood mononuclear cell, PBMC • phycoerythrin, PE • protein kinase C, PKC • tumor necrosis factor, TNF

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