CD66a, also called biliary glycoprotein (BGP), is a member of the carcinoembryonic antigen (CEA) family and of the immunoglobulin superfamily. CD66a is the human homologue of Cell-CAM, a well-defined cell adhesion molecule of the rat. In the present study a monoclonal antibody specific for CD66a was used to locate CD66a in human tissues. CD66a is expressed in epithelia, in certain endothelia, and in cells of the myeloid lineage. Hepatocytes were stained along the bile canaliculi. A characteristic apical membranous staining was observed in enterocytes, superficial absorptive cells of the colon, in the epithelia of esophageal and Brunner's glands, bile ducts and gallbladder, pancreatic ducts, proximal tubules of the kidney, prostate, endometrium, and mammary ducts. Selective staining of endothelia was present in glomeruli and vasa recta of the kidney, small placental vessels, adrenal sinusoids, endometrium, the prostate. Among the cells of the myeloid lineage, granulocytes and myelocytes were positive. The expression of CD66a by human cells and tissues is well comparable with the expression reported for Cell-CAM, the rat counterpart of CD66a. The wide tissue distribution of CD66a indicates that CD66a is a prominent human adhesion molecule.

Early brain development is characterised by the proliferation of neural precursor cells. Several families of signalling molecules such as the fibroblast growth factors (FGFs) and Wnts are known to play important roles in this early phase of brain development. Accumulating evidence demonstrates that signalling of these molecules requires the presence of heparan sulfate chains attached to a proteoglycan core protein (HSPG). However, the specific identity of the HSPG components in the developing brain is unknown. To determine which HSPGs might be involved at this early phase, we analysed the expression of the major cell surface HSPG families in the developing brain at a time of most active proliferation. Syndecan-1 and glypican-4 were the most highly expressed in the developing brain during the time of peak proliferation and localise to ventricular regions of the brain, where the precursor cells are proliferating. Syndecan-4, although less abundant, also localises to cells in the ventricular zone. We have also examined HSPG involvement in brain development using cultures of embryonic neural precursor cells. We find that FGF2 stimulation of proliferation is inhibited in the presence of sodium chlorate, an inhibitor of heparan sulfate synthesis, and is rescued by addition of exogenous heparan sulfate. These data support a requirement for heparan sulfate in FGF signalling for proliferation of brain precursor cells. The expression of these specific HSPGs within the proliferative zone of the brain suggests that they may be involved in regulation of early brain development, such as FGF-stimulated proliferation.

Objective. To investigate the role of interleukin-6 (IL-6) and transforming growth factor pl (TGFp1) in the regulation of tissue inhibitor of metalloproteinases-1 (TIMP-1) synthesis in human articular chondrocytes.Methods. Articular cartilage was obtained from human knee joints 24 hours after death. Chondrocytes were isolated by collagenase digestion and embedded in low-gellingtemperature agarose. After stimulation by cytokines, total RNA was isolated and analyzed by Northern blotting. TIMP-1 protein levels were determined using a competitive enzyme-linked immunosorbent assay.Results. Human chondrocytes in agarose culture expressed messenger RNA (mRNA) for the IL-6 receptor (gp80) and its signal-transducing subunit gp130. In contrast to the findings in a previous study, IL-6 did not stimulate TIMP-1 expression in these cells, whereas TGFPl was an important inducer of TIMP-1 mRNA and protein synthesis.Conclusion. Our findings suggest that TGFBl

Objective. To investigate the role of cytokines and growth factors in the regulation of hyaluronan synthesis in human synovial lining cells.Methods. Synovial lining cells were obtained from human knee joints, isolated by the explant method, and characterized by immunocytochemistry using monoclonal antibodies against monocytehnacrophage markers as well as antibodies against hyaluronan synthase. After stimulation by cytokines and growth factors, hyaluronan was measured by radiometric assay. The molecular weight distribution of the hyaluronan synthesized was determined by high-performance gelpermeation liquid chromatography. To test the effect of oxygen-derived free radicals, the concentration and molecular weight distribution of hyaluronan were determined in the presence and absence of catalase and superoxide dismutase.Results. Hyaluronan synthesis was stimulated in synovial lining cells by transforming growth factor Pl (TGFPl), interleukin-lp (IL-lp), and to a lesser extent by tumor necrosis factor a (TNFa). Analysis of the molecular weight distribution of hyaluronan after stimulation of synovial lining cells with TGFP1, IL-lP, and TNFa indicated that hyaluronan is synthesized in a high molecular weight form and might be degraded in the course of inflammatory processes by oxygen-derived free radicals. Conclusion. Our findings suggest that TGFPl is aSupported in part by grant 01 VM 891516 from the Bundesminister fur Forschung und Technologie (BMFT),