OSCAR Is a Receptor for Surfactant Protein D That Activates TNF-\alpha Release from Human CCR2+ Inflammatory Monocytes
J. Immunol. 194, 3317 - 3326. (2015)
Barrow, A.D., Palarasah, Y., Bugatti, M., Holehouse, A.S., Byers, D.E., Holtzman, M.J., Vermi, W., Skjødt, K., Crouch, E., and Colonna, M.
In this work, we used sequence analysis to identify a set of proteins with putative binding motifs for the osteoclast-associated receptor (OSCAR). OSCAR is expressed by osteoclasts, and binds to collagen on exposed bone to drive osteoclastogenesis. However, in humans, OSCAR is also expressed on monocytes, macrophages, and dendritic cells suggesting a role in the immune response. We identified a set of outative binding targets known to be involved in the to including SP-D, an immune response protein found in lung surfactant and part of the first line of defense against pulmonary pathogens. Further in vitro and in vivo work showed that OSCAR is indeed a bona fide myeloid immunoreceptor for SP-D, expressed by alveolar macrophages and CCR2+ monotytes. Furthermore, binding of SP-D to OSCAR triggers the release of TNF-\alpha. This demonstrates a novel new function of both OSCAR and SP-D and helps explain how SP-D drives the innate immune response. It also suggests a network of putative additional interaction partners, which are currently being explored through ongoing work.