Scavenger Receptors SR-AI/II and MARCO limit pulmonary dendritic cell migration and allergic airway inflammation.

Abstract

The class A scavenger receptors (SR-A) MARCO and SR-AI/II are expressed on lung macrophages (MPhis) and dendritic cells (DCs) and function in innate defenses against inhaled pathogens and particles. Increased expression of SR-As in the lungs of mice in an OVA-asthma model suggested an additional role in modulating responses to an inhaled allergen. After OVA sensitization and aerosol challenge, SR-AI/II and MARCO-deficient mice exhibited greater eosinophilic airway inflammation and airway hyperresponsiveness compared with wild-type mice. A role for simple SR-A-mediated Ag clearance ("scavenging") by lung MPhis was excluded by the observation of a comparable uptake of fluorescent OVA by wild-type and SR-A-deficient lung MPhis and DCs. In contrast, airway instillation of fluorescent Ag revealed a significantly higher traffic of labeled DCs to thoracic lymph nodes in SR-A-deficient mice than in controls. The increased migration of SR-A-deficient DCs was accompanied by the enhanced proliferation in thoracic lymph nodes of adoptively transferred OVA-specific T cells after airway OVA challenge. The data identify a novel role for SR-As expressed on lung DCs in the down-regulation of specific immune responses to aeroallergens by the reduction of DC migration from the site of Ag uptake to the draining lymph nodes.

• Authors: Mohamed S Arredouani, Francesca Franco, Amy Imrich, Alexey Fedulov, Xin Lu, David Perkins, Raija Soininen, Karl Tryggvason, Steven D Shapiro, Lester Kobzik
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 178 Issue 9 Pg. 5912-20 (May 01 2007) ISSN: 0022-1767 [Print] United States
• PMID: 17442975 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Marco protein, mouse
• Receptors, Immunologic
• Scavenger Receptors, Class A
• Ovalbumin

Topics

• Animals
• Asthma (genetics, immunology, pathology)
• Cell Movement
• Dendritic Cells (immunology)
• Disease Models, Animal
• Gene Expression
• Lung (immunology, pathology)
• Mice
• Mice, Mutant Strains
• Ovalbumin (immunology)
• Pneumonia (genetics, immunology, pathology)
• Receptors, Immunologic (genetics, physiology)
• Respiratory Hypersensitivity (genetics, immunology, pathology)
• Scavenger Receptors, Class A (genetics, physiology)
• T-Lymphocytes (immunology)