Neurothelin: an inducible cell surface glycoprotein of blood-brain barrier-specific endothelial cells and distinct neurons.

Abstract

Abstract. The blood-brain barrier is characterized by still poorly understood barrier and transport functions performed by specialized endothelial cells. Hybridoma technology has been used to identify a protein termed neurothelin that is specific for these endothelial cells. Neurothelin is defined by the species-specific mouse mAb lW5 raised against lentil-lectin-binding proteins of neural tissue from embryonic chick.In the posthatch chick, neurothelin expression is found on endothelial cells within the brain but not on those of the systemic vascular system. Injection of the monoclonal antibody in vivo leads to labeling of brain capillaries, indicating that the corresponding antigen is expressed on the luminal surface of brain endothelial cells. Transplantation of embryonic mouse brain onto the chick chorioallantoic membrane results in rodent brain vascularization by the avian vascular system. Subsequently, normally mAb lW5-negative endothelial cells, originating from blood vessels of the chick chorioallantoic membrane, are induced to express neurothelin when they are in contact with mouse neural tissue.In contrast to differentiated brain neurons that do not express neurothelin, neurons of the nonvascularized chick retina synthesize neurothelin. However, neurothelin is not found on retinal ganglion cell axons terminating on lW5-negative brain cells.lW5 immunoreactivity was also found in the pigment epithelium that forms the blood-eye barrier. Putting epithelial cells into culture results in concentration of neurothelin at cell-cell contact sites, leaving other cell surface areas devoid of antigen. Therefore, the distribution of neurothelin appears to be regulated by cell-cell interactions.In Western blot analysis, neurothelin was identified as a protein with a molecular mass of ,x,43 kD. The protein bears at least one intramolecular disulfide bridge and sulfated glucuronic acid as well as or-D-substituted mannose/glucose moieties.The exclusive neurothelin expression in the posthatch chick on endothelial cells of the central nervous system but not on systemic endothelial cells makes neurothelin a marker specific for blood-brain barrier-forming endothelial cells. The spatiotemporally regulated neurothelin expression in neurons suggests an interaction between vascularization and neuronal differentiation.

5A11 antigen is a cell recognition molecule which is involved in neuronal‐glial interactions in avian neural retina

“…In addition, the neural retina, pineal, brain endothelial cells, and blood cells show high immunostaining for the antigen in the mature chick (Fadool et al, 1990). Other descriptions of the distribution of HT7 and neurothelin have not noted the early generalized expression followed by broad localization to various epithelial structures (Risau et al, 1986;Schlosshauer and Herzog, 1990). The IW5 Mab for neurothelin also labels the optic nerve and ganglion cell fiber layer of the retina (Schlosshauer and Herzog, 19901, whereas both 5All and 3B7 Mabs show preferential labeling of Muller cell processes and end feet in these areas.…”

“…Based on these characteristics, Seulberger et al (1990) postulated that the HT7 antigen functions as a cell recognition molecule at the blood-brain barrier. The respective groups investigating the HT7 antigen and neurothelin have both noted high concentrations of the glycoprotein in chick retina although both laboratories seem to be concentrating their efforts on brain endothelial cells (Schlosshauer and Herzog, 1990;Seulberger et al, 1990). Our discovery of the 5All antigen occurred as the result of a concerted effort to identify cell recognition molecules that participate in the interactions between heterotypic cells of the embryonic neural retina (Linser et al, 1986;Linser and Perkins, 1987b).…”

“…Immunohistochemical analyses of retina tissue and isolated or cultured cells indicate that the 5 A l l antigen is distinct from other cell membrane antigens yet described in the retina system (Dobi et al, 1986;Lagenaur and Lemmon, 1987;Krotoski et al, 1986;Matsunaga et al, 1988), with the probable exception of the HT7 molecule (Schlosshauer and Herzog, 1990;Seulberger et al, 1990;see below). Figure 1 shows the distribution of Mab 5All binding relative to the distribution of the enzyme CA-I1 by double-label immunofluorescence.…”

Basigin (cd147) is expressed on melanoma cells and induces tumor cell invasion by stimulating production of matrix metalloproteinases by fibroblasts

“…1,2 Because of its broad distribution, it was expected that basigin plays fundamental roles in various physiologic processes. Molecules identical to basigin were subsequently identified and given different names: M6 3 and EMMPRIN 4 in human; HT7, 5 neurothelin 6 and 5A11 7 in chicken; gp42 8 in mouse; and OX-47 9 and CE9 10 in rat. Of them, EMMPRIN, previously termed TCSF, has been implicated in the induction of MMPs.…”

Selective Inhibition of T Cell Activation Via CD147 Through Novel Modulation of Lipid Rafts

“…Searching for molecules that might execute negative regulating signals via modification of GPI microdomains, we found CD147 to be a potential candidate. CD147, also known as M6 Ag (19), extracellular matrix metalloproteinase inducer (20), basigin or neurothelin (21,22), is a 50-to 60-kDa type I transmembrane glycoprotein belonging to the Ig superfamily (19). CD147 is widely expressed on hemopoietic and nonhemopoietic cells.…”