S-Endo-1 antigen (CD146), a transmembrane receptor also known as MUC18/MCAM, is a member of the immunoglobulin superfamily and belongs to a group of cell adhesion molecules. CD146 is highly expressed on the whole vascular tree. We demonstrate here that engagement of CD146 on human endothelial cells isolated from cord blood results in tyrosine phosphorylation of a large panel of cellular proteins, although no tyrosine phosphorylation of CD146 was detected.
A murine monoclonal antibody (mAb) S-Endo 1 has been produced to detect circulating endothelial cells detached from blood vessels in pathological conditions. We have demonstrated that the associated-antigen (S-Endo 1 Ag) was highly expressed on human vascular structure irrespective of tissue origin or vessel caliber. Its expression was not restricted to endothelium, since it was also detected at low level on smooth muscle cells, stroma cells and follicular dendritic cells. But its absence on hematopoietic cells made S-Endo 1 a helpful reagent to specifically discriminate endothelium from hematopoietic tissues. Biochemical characterization showed that S-Endo 1 recognizes a monomeric structure of approximately 118 kDa on cultured endothelial cells. S-Endo 1 was submitted to the 5th International Workshop (Boston, 1993) and did not cluster in any of the old or new endothelial clusters discussed at the conference, indicating its unique reactivity. Together with the data presented in this paper, this suggested that S-Endo 1 defines a previously undescribed endothelial molecule.
The idiopathic inflammatory myopathies (IIM), including dermatomyositis (DM), polymyositis (PM), and inclusion body myositis (IBM), are regarded as autoimmune diseases. They are characterized by chronic lymphocytic and macrophagic infiltration in muscle tissue. Of particular importance in understanding the immune response to IIM is the specific pattern of locally produced cytokines. Frozen muscle tissues from IIM (5 DM, 3 PM, and 1 IBM) were used to investigate the cytokine responses. The RT-PCR technique was instrumental to determine the pattern of expression of pro-inflammatory (IL-1 beta, IL-6, TNF-alpha), Th1 (IFN-gamma IL-2), and Th2 (IL-4) cytokines. Immunohistochemistry was also used to localize morphologically IFN-gamma and IL-4. Our results show that pro-inflammatory cytokines and Th1 cytokines are mainly expressed in IIM. The accumulation of mononuclear inflammatory cells and the inflammatory syndrome in IIM are probably related in part to the production of pro-inflammatory cytokines. Moreover, the pattern of local cytokine expression is consistent with a Th1 immune response related to autoimmune diseases.
We previously identified the S-Endo 1-associated antigen (CD146), an endothelial member of the immunoglobulin superfamily with a characteristic V-V-C2-C2-C2 Ig domain structure. In cultured human endothelial cells, we investigated its biosynthesis by immunoprecipitation and pulse-chase labeling. CD146 was synthesized as a 100 kDa precursor form, which was processed into a 120 kDa mature form. In the culture media of endothelial cells, we observed a CD146 soluble form that was about 10 kDa smaller than cell-associated CD146. In parallel with soluble forms of other members of the immunoglobulin superfamily, soluble CD146 could modulate and control the functions of the molecule.z 1998 Federation of European Biochemical Societies.
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