Characterization of a Novel Protein – 3D10 – a Secreted Receptor Form of the Human Osteoclast-Associated Receptor (OSCAR)

Human osteoclast-associated receptor (hOSCAR) is a member of the leukocyte receptor cluster (LRC) for an unknown ligand. hOSCAR has been reported to be expressed in several mononuclear cells (MNC) of myeloid origin and plays a role in modulating innate and adaptive immune response. We identified an alternative spliced isoform of hOSCAR that we had originally named 3D10. Sequence analysis showed that hOSCAR is expressed as membrane-bound (hOSCARm) and soluble (hOSCARs) isoforms with a non-spliced intron resulting in larger transcripts and soluble proteins lacking the trans-membrane domain. The expression profiles and tissue distribution of hOSCARm and hOSCARs were compared using specific PCR primers and new antibodies made in rabbits against either all or hOSCARs isoforms. Both isoforms were found to be differentially expressed in a wide variety of tissues. They were also found to be expressed in all MNC and neutrophils. hOSCARm isoforms appeared to be down-regulated more than the hOSCARs isoforms following stimulation of MNC with the mitogens PWM, Con A and PHA. Studies using THP-1 cells showed that the soluble isoforms are secreted and are up-regulated by both PMA and LPS. In conclusion, hOSCARs isoforms represent novel secretory isoforms of hOSCAR that may be functioning as decoy receptors.