HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Arredouani, M. S. Articles by Kobzik, L. Search for Related Content PubMed PubMed Citation Articles by Arredouani, M. S. Articles by Kobzik, L. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Substance via MeSH Medline Plus Health Information Asthma

Scavenger Receptors SR-AI/II and MARCO Limit Pulmonary Dendritic Cell Migration and Allergic Airway Inflammation¹

Mohamed S. Arredouani^2,3,*, Francesca Franco^3,,, Amy Imrich^*, Alexey Fedulov^*, Xin Lu, David Perkins^¶, Raija Soininen^||, Karl Tryggvason^#, Steven D. Shapiro and Lester Kobzik^4,*

^* Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115; Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115; Clinica di Malattie dell’Apparato Respiratorio, Dipartimento Integrato di Oncologia ed Ematologia, Università degli Studi di Modena e Reggio Emilia, Modena, Italy; Department of Family and Preventive Medicine, University of California San Diego, CA 92101; ^¶ Department of Medicine, University of California San Diego, CA 92101; ^|| Department of Medical Biochemistry and Molecular Biology, Biocenter Oulu, University of Oulu, Oulu, Finland; and ^# Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden

The class A scavenger receptors (SR-A) MARCO and SR-AI/II are expressed on lung macrophages (Ms) 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 Ms was excluded by the observation of a comparable uptake of fluorescent OVA by wild-type and SR-A-deficient lung Ms 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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants ES0002 and ES11008, and by Department of Defense Grant W81XWH-06-1-0289. M.S.A. is a recipient of the Jere Mead fellowship.

² Current address: Beth Israel Deaconess Medical Center, Harvard Medical School, 77 Avenue Louis Pasteur, HIM-1039, Boston, MA 02115.

³ M.S.A. and F.F. contributed equally to this work.

⁴ Address correspondence and reprint requests to Dr. Lester Kobzik, Department of Environmental Health, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115. E-mail address: lkobzik{at}hsph.harvard.edu

⁵ Abbreviations used in this paper: SR, scavenger receptor; SR-AI/II, SR class A, type I and type II; AHR, airway hyperresponsiveness; AM, alveolar macrophage; BAL, bronchoalveolar lavage; BALF, BAL fluid; Ct, threshold cycle; C3H, C3H/HeJ; DC, dendritic cell; i.t., intratracheal; KO, knockout; LN, lymph node; MARCO, macrophage receptor with collagenous structure; M, macrophage; P_enh, enhanced pause; WT, wild type.

This article has been cited by other articles:

				C. Sorio and P. Melotti Editorial: The role of macrophages and their scavenger receptors in cystic fibrosis J. Leukoc. Biol., September 1, 2009; 86(3): 465 - 468. [Full Text] [PDF]

				R. Takamiya, C.-C. Hung, S. R. Hall, K. Fukunaga, T. Nagaishi, T. Maeno, C. Owen, A. A. Macias, L. E. Fredenburgh, A. Ishizaka, et al. High-Mobility Group Box 1 Contributes to Lethality of Endotoxemia in Heme Oxygenase-1-Deficient Mice Am. J. Respir. Cell Mol. Biol., August 1, 2009; 41(2): 129 - 135. [Abstract] [Full Text] [PDF]

				K. Nakagome, K. Okunishi, M. Imamura, H. Harada, T. Matsumoto, R. Tanaka, J.-i. Miyazaki, K. Yamamoto, and M. Dohi IFN-{gamma} Attenuates Antigen-Induced Overall Immune Response in the Airway As a Th1-Type Immune Regulatory Cytokine J. Immunol., July 1, 2009; 183(1): 209 - 220. [Abstract] [Full Text] [PDF]