OSCAR is a receptor for surfactant protein D that activates TNF-α release from human CCR2+ inflammatory monocytes

Alexander D. Barrow, Yaseelan Palarasah, Mattia Bugatti, Alex S. Holehouse, Derek E. Byers, Michael J. Holtzman, William Vermi, Karsten Skjødt, Erika Crouch, Marco Colonna

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Surfactant protein D (SP-D) is critical for maintenance of lung homeostasis and provides a first line of defense to pathogens at mucosal surfaces. Polymorphisms in the P-D - encoding gene SFTPD have been associated with chronic obstructive pulmonary disease and ulcerative colitis. Identification of the immunoreceptors that bind SP-D is essential for understanding its contribution to lung homeostasis and mucosal defense. We located a putative binding motif for the osteoclast-associated receptor (OSCAR) within the SP-D collagenous domain. An OSCAR-Fc fusion protein specifically bound to the collagenous region of recombinant SP-D and captured native SP-D from human bronchoalveolar lavage. OSCAR localized in an intracellular compartment of alveolar macrophages together with SP-D. Moreover, we found OSCAR on the surface of interstitial lung and blood CCR2+inflammatory monocytes, which secreted TNF-α when exposed to SP-D in an OSCAR-dependent fashion. OSCAR and SP-D did not exclusively colocalize in lung, as they were also highly expressed in atherosclerotic plaques of human aorta, supporting a role for this interaction in atherosclerosis. Our results identify the OSCAR:SP-D interaction as a potential therapeutic target in chronic inflammatory diseases of the lung as well as other diseases involving tissue accumulation of SP-D, infiltration of inflammatory monocytes, and release of TNF-α.

Original languageEnglish
Pages (from-to)3317-3326
Number of pages10
JournalJournal of Immunology
Volume194
Issue number7
DOIs
StatePublished - Apr 1 2015

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