The late asthmatic response is linked with increased surface tension and reduced surfactant protein B in mice.

Abstract

Pulmonary surfactant dysfunction may significantly contribute to small airway obstruction during the asthmatic response, but neither its exact role nor its regulation is clear. Surfactant function and composition was studied in an Aspergillus fumigatus (Af)-induced late-phase allergic airway response in sensitized BALB/c mice. The peak of Af-induced airway hyperresponsiveness in sensitized and challenged mice 24 h after allergen provocation coincided with a significant fall in surface activity of the pulmonary surfactant. The underlying changes included time-dependent elaboration of eotaxin and IL-5 followed by eosinophil influx into the airways. The height of airway inflammation and hyperresponsiveness was preceded by release of IL-4 and marked reductions in surfactant protein (SP)-B, a hydrophobic surfactant protein responsible for maintaining low surface tension of the lining fluid of distal air spaces. Furthermore, intratracheal administration of IL-4 significantly inhibited SP-B, indicating a regulatory role of this cytokine in the surfactant biophysical changes. Thus surfactant dysfunction induced by an IL-4-driven SP-B deficiency after allergen provocation may be an important part of the late asthmatic airway response.

• Authors: Angela Haczku, Elena N Atochina, Yaniv Tomer, Yang Cao, Colleen Campbell, Seth T Scanlon, Scott J Russo, Goran Enhorning, Michael F Beers
• Journal: American journal of physiology. Lung cellular and molecular physiology (Am J Physiol Lung Cell Mol Physiol) Vol. 283 Issue 4 Pg. L755-65 (Oct 2002) ISSN: 1040-0605 [Print] United States
• PMID: 12225952 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• CCL11 protein, human
• Ccl11 protein, mouse
• Chemokine CCL11
• Chemokines, CC
• Interleukin-5
• Proteolipids
• Pulmonary Surfactants
• RNA, Messenger
• STAT6 Transcription Factor
• STAT6 protein, human
• Stat6 protein, mouse
• Trans-Activators
• Interleukin-4

Topics

• Animals
• Aspergillosis, Allergic Bronchopulmonary (immunology, metabolism)
• Aspergillus fumigatus (immunology)
• Asthma (immunology, metabolism)
• Bronchial Hyperreactivity (immunology, metabolism)
• Bronchoalveolar Lavage Fluid (chemistry, immunology)
• Chemokine CCL11
• Chemokines, CC (metabolism)
• Eosinophils (immunology)
• Female
• Humans
• Hypersensitivity (immunology, metabolism)
• Interleukin-4 (metabolism)
• Interleukin-5 (metabolism)
• Kinetics
• Mice
• Mice, Inbred BALB C
• Mice, Mutant Strains
• Proteolipids (genetics, metabolism)
• Pulmonary Surfactants (genetics, metabolism)
• RNA, Messenger (analysis)
• STAT6 Transcription Factor
• Surface Tension
• Trans-Activators (genetics)
• Transcription, Genetic (physiology)