Soluble CD276 (B7-H3) is released from monocytes, dendritic cells and activated T cells and is detectable in normal human serum.
Expression of membrane CD276 (mB7-H3) has been reported on dendritic cells (DCs), monocytes, activated T cells, and various carcinoma cells. However, reports concerning its in vivo function have been inconsistent. Moreover, whether there is a soluble form of this protein is not known. In this study, using a sensitive dual monoclonal antibody sandwich enzyme-linked immunosorbent assay (ELISA) to detect the soluble form of B7-H3 (sB7-H3), we demonstrated the release of sB7-H3 by monocytes, DCs, activated T cells, and various mB7-H3+ but not mB7-H3- carcinoma cells. Release from cells was blocked by addition of a matrix metalloproteinase inhibitor (MMPI), which concomitantly caused the accumulation of B7-H3 on the cell surface. To determine the level of circulating sB7-H3, more than 200 serum samples were included in the study. The results indicated that sB7-H3 was present at high levels in all serum samples. Western blotting of sB7-H3 from cell culture supernatants or sera of healthy donors indicated that the molecular size was approximately 16 kDa. Soluble B7-H3 was able to bind to the B7-H3 receptor (B7-H3R) on activated T cells, which showed that sB7-H3 is a functionally active form. These results indicate that release of sB7-H3 from the cell surface is mediated by a matrix metalloproteinase and probably regulates B7-H3R/B7-H3 interactions in vivo. Cleavage of sB7-H3 to an active soluble form would alter both proximal and distal cellular responses.
Zhang
Guangbo
G
Clinical Immunology Laboratory, Suzhou University no. 1 Affiliated Hospital, Suzhou, China.
Hou
Jianquan
J
Shi
Jinfang
J
Yu
Gehua
G
Lu
Binfeng
B
Zhang
Xueguang
X
D015703:Antigens, CD / Q000097:blood*; D060887:B7 Antigens; D015153:Blotting, Western; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D020781:Matrix Metalloproteinase 1 / Q000502:physiology; D009000:Monocytes / Q000276:immunology*; D011971:Receptors, Immunologic / Q000097:blood*; D012995:Solubility; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D060887:B7 Antigens; C423237:CD276 protein, human; D008024:Ligands; D011971:Receptors, Immunologic; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1