Respiratory syncytical virus-induced chemokine expression in the lower airways: eosinophil recruitment and degranulation

Am J Respir Crit Care Med. 1999 Jun;159(6):1918-24. doi: 10.1164/ajrccm.159.6.9805083.


Characterization of chemokine expression patterns in virus-infected epithelial cells provides important clues to the pathophysiology of such infections. The aim of this study was to determine the chemokine response pattern of respiratory epithelium when infected with respiratory syncytial virus (RSV). Macrophage inflammatory protein-1-alpha (MIP-1-alpha), interleukin-8 (IL-8), and RANTES concentrations were measured from RSV-infected HEp-2, MRC-5, and WI-38 cell culture supernatants daily following infection. Additionally, MIP-1-alpha, IL-8, and RANTES concentrations were measured from lower respiratory secretions obtained from 10 intubated infants (0-24 mo) with RSV bronchiolitis, and from 10 control subjects. Our results indicate that respiratory epithelial cells respond to RSV infection by producing MIP-1-alpha, IL-8, and RANTES. Production of MIP-1-alpha required ongoing viral replication, whereas RANTES and IL-8 could be elicited by inactivated forms of the virus. MIP-1-alpha, RANTES, and IL-8 were also present in lower airway secretions obtained from patients with RSV bronchiolitis. Eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN), the eosinophil secretory ribonucleases, were detected in lower airway secretions from RSV-infected patients; ECP concentrations correlated with MIP-1-alpha concentrations (r = 0.93). We conclude that MIP-1-alpha is present in the lower airways during severe RSV disease. The correlation between MIP-1-alpha and ECP concentrations suggests a role for eosinophil degranulation products in the pathogenesis of RSV bronchiolitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Proteins / biosynthesis
  • Cell Degranulation / physiology
  • Cell Line / virology
  • Chemokine CCL4
  • Chemokine CCL5 / metabolism
  • Chemokines / metabolism*
  • Eosinophil Granule Proteins
  • Eosinophil-Derived Neurotoxin
  • Eosinophils / physiology
  • Epithelial Cells / metabolism
  • Humans
  • Interleukin-8 / metabolism
  • Macrophage Inflammatory Proteins / biosynthesis
  • Peroxidase / metabolism
  • Proteins / metabolism
  • Respiratory Syncytial Virus Infections / metabolism*
  • Respiratory Syncytial Virus Infections / pathology
  • Respiratory Syncytial Viruses / physiology
  • Respiratory System / metabolism*
  • Respiratory System / pathology
  • Ribonucleases*
  • Virus Activation / physiology


  • Blood Proteins
  • Chemokine CCL4
  • Chemokine CCL5
  • Chemokines
  • Eosinophil Granule Proteins
  • Interleukin-8
  • Macrophage Inflammatory Proteins
  • Proteins
  • Peroxidase
  • Eosinophil-Derived Neurotoxin
  • Ribonucleases