Pulmonary arterial remodeling induced by a Th2 immune response.

Abstract

Pulmonary arterial remodeling characterized by increased vascular smooth muscle density is a common lesion seen in pulmonary arterial hypertension (PAH), a deadly condition. Clinical correlation studies have suggested an immune pathogenesis of pulmonary arterial remodeling, but experimental proof has been lacking. We show that immunization and prolonged intermittent challenge via the airways with either of two different soluble antigens induced severe muscularization in small- to medium-sized pulmonary arteries. Depletion of CD4(+) T cells, antigen-specific T helper type 2 (Th2) response, or the pathogenic Th2 cytokine interleukin 13 significantly ameliorated pulmonary arterial muscularization. The severity of pulmonary arterial muscularization was associated with increased numbers of epithelial cells and macrophages that expressed a smooth muscle cell mitogen, resistin-like molecule alpha, but surprisingly, there was no correlation with pulmonary hypertension. Our data are the first to provide experimental proof that the adaptive immune response to a soluble antigen is sufficient to cause severe pulmonary arterial muscularization, and support the clinical observations in pediatric patients and in companion animals that muscularization represents one of several injurious events to the pulmonary artery that may collectively contribute to PAH.

• Authors: Eleen Daley, Claire Emson, Christophe Guignabert, Rene de Waal Malefyt, Jennifer Louten, Viswanath P Kurup, Cory Hogaboam, Laimute Taraseviciene-Stewart, Norbert F Voelkel, Marlene Rabinovitch, Ekkehard Grunig, Gabriele Grunig
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 205 Issue 2 Pg. 361-72 (Feb 18 2008) ISSN: 1540-9538 [Electronic] United States
• PMID: 18227220 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Fungal
• Interleukin-13
• Interleukin-4
• Ovalbumin

Topics

• Animals
• Antigens, Fungal (immunology)
• Aspergillus fumigatus (immunology)
• Blood Pressure
• Heart Ventricles (physiopathology)
• Immunization
• Interleukin-13 (immunology)
• Interleukin-4 (deficiency, genetics, immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Ovalbumin (immunology)
• Pulmonary Artery (immunology, pathology)
• Th2 Cells (immunology)