Isolation of a Human Homolog of Osteoclast Inhibitory Lectin That Inhibits the Formation and Function of Osteoclasts

Hu, Yun; Zhou, Hong; Myers, Damian E.; Quinn, Julian M.W.; Atkins, Gerald J.; Ly, Chi; Gange, C; Kartsogiannis, Vicky; Elliott, Jan; Kostakis, Panagiota; Zannettino, Andrew C.W.; Cromer, Brett A.; McKinstry, William J.; Findlay, David M.; Gillespie, Matthew T.; Ng, Kong Wah

doi:10.1359/jbmr.0301215

Cited by 42 publications

(35 citation statements)

References 32 publications

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“…Previous work suggested that LLT1 mRNA is expressed in osteoblast cell lines and that LLT1 transcript levels increased with IL-1␣ treatment (23). A prior report also demonstrated that PMAstimulated PBMC express LLT1 mRNA (24).…”

Section: Stimulation Through Tlr3 Tlr4 Tlr7 Tlr7 or Tlr9 Induces mentioning

confidence: 92%

Functional Consequences of Interactions between Human NKR-P1A and Its Ligand LLT1 Expressed on Activated Dendritic Cells and B Cells

Rosen

Cao

Avery

et al. 2008

The Journal of Immunology

149

196

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Lectin-like transcript-1 (LLT1) (also named osteoclast inhibitory lectin or CLEC2D) is a ligand for the human NKR-P1A (CD161) receptor, present on NK cells and T cells. To further understand the physiological relevance of this interaction, we developed mAbs against LLT1, characterized the expression pattern of LLT1, and explored the functional consequence of LLT1 engagement of the NKR-P1A receptor on NK cells and T cells. LLT1 is expressed on TLR-activated plasmacytoid dendritic, TLR-activated monocyte-derived dendritic cells, and on B cells stimulated through TLR9, surface Ig, or CD40. Interactions between NKR-P1A on NK cells and LLT1 on target cells inhibit NK cell-mediated cytotoxicity and cytokine production and can inhibit TNF-α production by TCR-activated NKR-P1A+ CD8+ T cells. In contrast, NKR-P1A failed to inhibit or augment the TCR-dependent activation of NKR-P1A-bearing CD4+ T cells. Expression of LLT1 on activated dendritic cells and B cells suggests that it might regulate the cross-talk between NK cells and APCs.

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Section: Stimulation Through Tlr3 Tlr4 Tlr7 Tlr7 or Tlr9 Induces mentioning

confidence: 92%

Functional Consequences of Interactions between Human NKR-P1A and Its Ligand LLT1 Expressed on Activated Dendritic Cells and B Cells

Rosen

Cao

Avery

et al. 2008

The Journal of Immunology

149

196

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“…Production of recombinant GST, GST-mOCIL, and GST-hOCIL was carried out as described previously (2). Briefly, DNA sequences corresponding to the extracellular domains of mOCIL (residues 76 -207) and hOCIL (residues 71-191) were amplified and inserted into the pGEX-2T plasmid, and the proteins were expressed in Escherichia coli BL21, resulting in proteins with N-terminal GST tags.…”

Section: Materials-d(ϩ)-glucose and D-maltose Were Purchased From Merckmentioning

confidence: 99%

“…acts as an inhibitor of osteoclastogenesis in vitro (1,2). Originally identified in osteoblasts, OCIL mRNA levels are regulated by many osteotropic hormones and cytokines.…”

mentioning

confidence: 99%

“…Murine OCIL (also known as CLR-b for C-type lectin-related molecule-b) (3) is widely expressed in most tissues, notably in epithelial and mesenchymal cells, but also in dendritic, macrophage, and lymphocyte populations (1,4,5). OCIL is a member of a small family of related proteins that includes murine OCILrP1 and murine OCILrP2 (also called CLR-g) (6), and one human homolog has also been identified (2). We have previously shown that the soluble recombinant C-type lectin domains of each of these molecules inhibit osteoclast formation with similar potency (1,2,6).…”

mentioning

confidence: 99%

“…OCIL is a member of a small family of related proteins that includes murine OCILrP1 and murine OCILrP2 (also called CLR-g) (6), and one human homolog has also been identified (2). We have previously shown that the soluble recombinant C-type lectin domains of each of these molecules inhibit osteoclast formation with similar potency (1,2,6).…”

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confidence: 99%

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Characterization of Sugar Binding by Osteoclast Inhibitory Lectin

Gange

Quinn

Zhou

et al. 2004

Journal of Biological Chemistry

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Osteoclast inhibitory lectin (OCIL) is a membranebound C-type lectin that blocks osteoclast differentiation and, via binding to its cognate receptor NKRP1D, inhibits natural killer cell-mediated cytotoxicity. OCIL is a member of the natural killer cell receptor C-type lectin group that includes CD69 and NKRP1D. We investigated carbohydrate binding of soluble recombinant human and mouse OCIL in enzyme-linked immunosorbent assay-based assays. OCIL bound immobilized high molecular weight sulfated glycosaminoglycans, including fucoidan, -carrageenan, and dextran sulfate, but not unsulfated dextran or sialated hyaluronic acid. Carbohydrate binding was Ca 2؉ -independent. Binding of immobilized low molecular weight glycosaminoglycans, including chondroitin sulfate (A, B, and C forms) and heparin, was not observed. However, the soluble forms of these low molecular weight glycosaminoglycans competed for OCIL binding of immobilized fucoidan (as did soluble fucoidan, dextran sulfate, and -carrageenan), indicating that OCIL does recognize these carbohydrates. Inhibition constants for chondroitin sulfate A and heparin binding were 380 and 5 nM, respectively. Immobilized and soluble monosaccharides did not bind OCIL. The presence of saturating levels of fucoidan, dextran sulfate, and -carrageenan did not affect OCIL inhibition of osteoclast formation. The fucoidan-binding lectins Ulex europaeus agglutinin I and Anguilla anguilla agglutinin did not block osteoclast formation or affect the inhibitory action of OCIL. Although the osteoclast inhibitory action of OCIL is independent of sugar recognition, we have found that OCIL, a lectin widely distributed, but notably localized in bone, skin, and other connective tissues, binds a range of physiologically important glycosaminoglycans, and this property may modulate OCIL actions upon other cells.

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Cloning and analysis of rat osteoclast inhibitory lectin gene promoter

Quan

Zheng

et al. 2009

J of Cellular Biochemistry

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Osteoclast inhibitory lectin (OCIL) is a novel regulator of bone remodeling, however, little is known concerning how OCIL is regulated to date. In this study, approximately 4.4 kb of the 5'-flanking sequence of rat OCIL gene was cloned into the promoter-less reporter vector pGL3-basic and transiently transfected into three different cell lines. The differences in the levels of luciferase activity paralleled well with the levels of OCIL mRNA expression in these cells, suggesting that the regulation of rat OCIL gene expression occurs mainly at the transcriptional level. Additional luciferase assays using a series of constructs containing unidirectionally deleted fragments showed that the construct-1819/pGL3 (-1819 to +118) exhibited the highest luciferase activity, suggesting the presence of functional promoter in this region. The region from -4370 to -2805 might contain negative regulatory elements, while the region from -1819 to -1336 might have important positive regulatory elements that enhance OCIL transcription. Sequence analysis of the promoter revealed the absence of both TATA and CAAT boxes. However, in the proximal promoter region (-81 to +118), several potential transcription factor binding sites that may be responsible for the basal transcriptional activity of rat OCIL promoter were observed. The promoter contains several potential Sp1 binding sites, and cotransfection of a shRNA expression plasmid that knockdowns Sp1 significantly reduced OCIL promoter activity and endogenous gene expression and moreover, overexpressing Sp7, a Sp1 family member that also binds to Sp1 binding sequence, increased OCIL promoter activity and gene expression, suggesting a role of Sp1 family proteins in regulation of OCIL transcription.

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Isolation of a Human Homolog of Osteoclast Inhibitory Lectin That Inhibits the Formation and Function of Osteoclasts

Cited by 42 publications

References 32 publications

Functional Consequences of Interactions between Human NKR-P1A and Its Ligand LLT1 Expressed on Activated Dendritic Cells and B Cells

Functional Consequences of Interactions between Human NKR-P1A and Its Ligand LLT1 Expressed on Activated Dendritic Cells and B Cells

Characterization of Sugar Binding by Osteoclast Inhibitory Lectin

Cloning and analysis of rat osteoclast inhibitory lectin gene promoter

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