OSCAR is a receptor for surfactant protein D that activates TNF-α release from human CCR2+ inflammatory monocytes.
Alexander D BarrowYaseelan PalarasahMattia BugattiAlex S HolehouseDerek E ByersMichael J HoltzmanWilliam VermiKarsten SkjødtErika CrouchMarco ColonnaPublished in: Journal of immunology (Baltimore, Md. : 1950) (2015)
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 SP-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.
Keyphrases
- chronic obstructive pulmonary disease
- endothelial cells
- rheumatoid arthritis
- dendritic cells
- oxidative stress
- ulcerative colitis
- type diabetes
- escherichia coli
- peripheral blood
- risk assessment
- immune response
- induced pluripotent stem cells
- transcription factor
- staphylococcus aureus
- climate change
- protein protein
- pulmonary hypertension
- multidrug resistant
- small molecule
- copy number
- pulmonary arterial hypertension
- antimicrobial resistance
- gram negative
- amino acid
- genome wide analysis