Cell-Specific Expression of RANTES, MCP-1, and MIP-1α by Lower Airway Epithelial Cells and Eosinophils Infected with Respiratory Syncytial Virus

Abstract

Respiratory syncytial virus (RSV) is the major cause of acute bronchiolitis in infancy, a syndrome characterized by wheezing, respiratory distress, and the pathologic findings of peribronchial mononuclear cell infiltration and release of inflammatory mediators by basophil and eosinophil leukocytes. Composition and activation of this cellular response are thought to rely on the discrete target cell selectivity of C-C chemokines. We demonstrate that infection in vitro of human epithelial cells of the lower respiratory tract by RSV induced dose- and time-dependent increases in mRNA and protein secretion for RANTES (regulated upon activation, normal T-cell expressed and presumably secreted), monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1α (MIP-1α). Production of MCP-1 and MIP-1α was selectively localized only in epithelial cells of the small airways and lung. Exposure of epithelial cells to gamma interferon (IFN-γ), in combination with RSV infection, induced a significant increase in RANTES production that was synergistic with respect to that obtained by RSV infection or IFN-γ treatment alone. Epithelial cell-derived chemokines exhibited a strong chemotactic activity for normal human blood eosinophils. Furthermore, eosinophils were susceptible to RSV and released RANTES and MIP-1α as a result of infection. Therefore, the inflammatory process in RSV-induced bronchiolitis appears to be triggered by the infection of epithelial cells and further amplified via mechanisms driven by IFN-γ and by the secretion of eosinophil chemokines.

Rhinovirus infection up‐regulates eotaxin and eotaxin‐2 expression in bronchial epithelial cells

“…This chemokine may not be secreted by BEAS-2B cells or its levels may have been lower than the sensitivity of the assay. Nevertheless, MIP-1a is up-regulated in primary bronchial epithelial cells infected with respiratory syncytial virus [13].…”

Effects of respiratory syncytial virus infection and major basic protein derived from eosinophils in pulmonary alveolar epithelial cells (A549)

“…In general, virus-stimulated immunological cells (T cells and macrophages) and virus-infected airway cells/tissues produce many types of cytokines/chemokines, and these immunological responders may induce inflammatory responses in vivo (Kimpen et al, 1996;Schwarze et al, 1997;Olszewska-Pazdrak et al, 1998;Kato et al, 2005). The surface of RSV particles contains some major antigens, such as F (fusion) protein, G (glycoprotein) and SH (small hydrophobic) proteins (Collins and Crowe, 2007).…”

Respiratory syncytial virus and neutrophil activation

“…The very high numbers of neutrophils observed in the airways of infants with acute bronchiolitis appears to be a consequence of both recruitment and prolonged survival within the infant airways. In vitro studies have indicated that RSV infection results in the release of high concentrations of IL-8 and of other pro-inflammatory molecules including IL-1, TNF a , RANTES, MIP-1 a [9][10][11][12] and these finding reflect those from clinical studies involving infants with RSV infections [6,13,14] More recently it has been shown that there are factor(s) present within the infant airway which prolong neutrophil survival which will contribute to the observed neutrophilia [15].…”