Osteopontin mRNA is expressed by smooth muscle-derived foam cells in human atherosclerotic lesions of the aorta

Osteopontin is a phosphorylated, sialic acid-rich, noncollagenous bone matrix protein containing the Arg-Gly-Asp-Ser amino acid sequence responsible for cell adhesion. The protein strongly binds to hydroxyapatite and play an important role in calcification. Expression of osteopontin mRNA was analyzed in human aortic atherosclerotic lesion by Northern blot hybridization, as well as by in situ hybridization. The expression of osteopontin mRNA was detected in 24 out of 25 samples of aorta obtained from 17 autopsy cases, but not in one normal aortic sample. The magnitude of expression was proportional to the stage of atherosclerosis. In situ hybridization revealed that the cells expressing osteopontin mRNA were detected in the wall surrounding atheroma and closely associated with calcification. They were morphologically identified as foam cells and immunohistologically positive with HHF35, appearing to be derived from smooth muscle cells. These findings have suggested that smooth muscle cell-derived foam cells express osteopontin mRNA and play an important role in calcification of the atheroscleroti

Identification and expression of mouse Langerin (CD207) in dendritic cells

We have cloned the mouse homologue of human Langerin (h-Langerin), a type II transmembrane protein with a single external C-type lectin domain. Mouse Langerin (m-Langerin) displays 65 and 74% homologies in total amino acid and lectin domains with those of h-Langerin. The cognate mouse and rat genes were assigned to chromosome 6D1-D2 and chromosome 4q33 distal-q34.1 proximal respectively, syntenic to the h-Langerin gene on chromosome 2p13. With RT-PCR, m-Langerin transcripts were as expected detected in MHC class II+, but not MHC class II-, cells from epidermis and the expression level was reduced by culture. However, m-Langerin transcripts were also expressed in spleen, lymph nodes (LN), thymus, liver, lung and even heart, but not gut-associated lymphoid tissues. In single-cell lymphoid suspensions, m-Langerin transcripts were mainly detected in the CD11c(+) dendritic cells (DC), especially the CD11b(low)/CD8(high) fraction of spleen and LN. DC generated from bone marrow precursors by granulocyte macrophage colony stimulating factor (GM-CSF) expressed m-Langerin, but this was shut down during maturation with CD40 ligand or lipopolysaccharide. DC derived from blood monocytes by GM-CSF + IL-4 lacked m-Langerin unless the cultures were supplemented with transforming growth factor (TGF)-beta1. Unexpectedly, significant amounts of m-Langerin transcripts were detected in skin and LN of TGF-beta1-deficient mice, although in much lower amounts than littermate controls. Recombinant m-Langerin could form multimers and bind to mannan-agarose. These findings indicate that Langerin expression is regulated at several levels: by TGF-beta1, DC subsets, DC maturation and the tissue environmen