SP-A enhances viral clearance and inhibits inflammation after pulmonary adenoviral infection

Am J Physiol. 1999 Sep;277(3):L580-8. doi: 10.1152/ajplung.1999.277.3.L580.

Abstract

Surfactant protein A (SP-A) is a member of the collectin family of host defense molecules expressed primarily in the epithelial cells of the lung. To determine the role of SP-A in pulmonary adenoviral infection, SP-A-deficient (SP-A -/-) mice were intratracheally infected with a replication-deficient recombinant adenovirus, Av1Luc1. Lung inflammation was markedly increased in SP-A -/- compared with SP-A +/+ mice and was associated with increased hemorrhage and epithelial cell injury. Polymorphonuclear cells in bronchoalveolar lavage fluid (BALF) were increased in SP-A -/- mice after administration of adenovirus. Coadministration of adenovirus and purified human SP-A ameliorated adenoviral-induced lung inflammation in SP-A -/- mice. Concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and IL-1beta were increased in BALF of SP-A -/- mice. Likewise, TNF-alpha, IL-6, macrophage inflammatory protein (MIP)-1alpha, monocyte chemotactic protein-1, and MIP-2 mRNAs were increased in lung homogenates from SP-A -/- mice 6 and 24 h after viral administration. Clearance of adenoviral DNA from the lung and uptake of fluorescent-labeled adenovirus by alveolar macrophages were decreased in SP-A -/- mice. SP-A enhances viral clearance and inhibits lung inflammation during pulmonary adenoviral infection, providing support for the importance of SP-A in antiviral host defense.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviridae / isolation & purification*
  • Adenoviridae Infections / metabolism
  • Adenoviridae Infections / pathology
  • Adenoviridae Infections / physiopathology
  • Adenoviridae Infections / virology*
  • Animals
  • Bronchoalveolar Lavage Fluid / cytology
  • Cytokines / metabolism
  • Humans
  • Lung / metabolism
  • Lung / pathology
  • Lung / physiopathology
  • Lung / virology*
  • Macrophages, Alveolar / physiology
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout / genetics
  • Pneumonia / pathology
  • Pneumonia / prevention & control*
  • Proteolipids / genetics
  • Proteolipids / pharmacology
  • Proteolipids / physiology*
  • Pulmonary Surfactant-Associated Protein A
  • Pulmonary Surfactant-Associated Proteins
  • Pulmonary Surfactants / genetics
  • Pulmonary Surfactants / pharmacology
  • Pulmonary Surfactants / physiology*

Substances

  • Cytokines
  • Proteolipids
  • Pulmonary Surfactant-Associated Protein A
  • Pulmonary Surfactant-Associated Proteins
  • Pulmonary Surfactants