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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vascular immunotargeting is a mean for a site-selective delivery of drugs and genes to endothelium. In this study, we compared recognition of pulmonary and systemic vessels in rats by candidate carrier monoclonal antibodies (MAbs) to endothelial antigens platelet endothelial cell adhesion molecule (PECAM)-1 (CD31), intercellular adhesion molecule (ICAM)-1 (CD54), Thy-1.1 (CD90.1), angiotensin-converting enzyme (ACE; CD143), and OX-43. Tissue immunostaining showed that endothelial cells were Thy-1.1 positive in capillaries but negative in large vessels. In the lung, anti-ACE MAb provided a positive staining in 100% capillaries vs. 5-20% capillaries in other organs. Other MAbs did not discriminate between pulmonary and systemic vessels. We determined tissue uptake after infusion of 1 microg of (125)I-labeled MAbs in isolated perfused lungs (IPL) or intravenously in intact rats. Uptake in IPL attained 46% of the injected dose (ID) of anti-Thy-1.1 and 20-25% ID of anti-ACE, anti-ICAM-1, and anti-OX-43 (vs. 0.5% ID of control IgG). However, after systemic injection at this dose, only anti-ACE MAb 9B9 displayed selective pulmonary uptake (16 vs. 1% ID/g in other organs). Anti-OX-43 displayed low pulmonary (0.5% ID/g) but significant splenic and cardiac uptake (7 and 2% ID/g). Anti-Thy-1.1 and anti-ICAM-1 displayed moderate pulmonary (4 and 6% ID/g, respectively) and high splenic and hepatic uptake (e.g., 18% ID/g of anti-Thy-1.1 in spleen). The lung-to-blood ratio was 5, 10, and 15 for anti-Thy-1.1, anti-ACE, and anti-ICAM-1, respectively. PECAM antibodies displayed low pulmonary uptake in perfusion (2% ID) and in vivo (3-4% ID/g). However, conjugation with streptavidin (SA) markedly augmented pulmonary uptake of anti-PECAM in perfusion (10-54% ID, depending on an antibody clone) and in vivo (up to 15% ID/g). Therefore, ACE-, Thy-1.1-, ICAM-1-, and SA-conjugated PECAM MAbs are candidate carriers for pulmonary targeting. ACE MAb offers a high selectivity of pulmonary targeting in vivo, likely because of a high content of ACE-positive capillaries in the lungs.
Am J Physiol Lung Cell Mol Physiol 2001 Jun
PMID:Lung uptake of antibodies to endothelial antigens: key determinants of vascular immunotargeting. 1135 Aug 15

Spindle cell melanoma is a rare and distinctive variant of malignant melanoma that is composed of spindled neoplastic cells and includes desmoplastic and neurotropic melanoma. The lack of expression of several melanoma markers may result in a delayed or wrong diagnosis. In this study, we have analyzed in detail the phenotype of the tumor cells in 9 spindle cell melanomas on both paraffin-embedded and frozen material, using melanocytic, neural, and mesenchymal markers. The neoplastic cells expressed the melanocytic markers S-100, Mel-CAM, and NKIC3, but lacked gp100 and Melan-A; tyrosinase and c-Kit were expressed in 2 of 7 cases. Most cases expressed the neural markers p75-nerve growth factor receptor, neural cell adhesion molecule, and NSE. All cases expressed vimentin but lacked the mesenchymal markers CD34 and alpha-smooth muscle actin. Remarkably, all spindle cell melanomas strongly and diffusely expressed the fibroblastic markers Thy1 (CD90) and aminopeptidase N (CD13) and variably expressed the enzyme prolyl-4-hydroxylase, involved in procollagen formation. The coexpression of melanocytic, neural, and fibroblastic markers suggests bidirectional differentiation of neoplastic melanocytes toward (myo)fibroblasts and Schwann cells, a feature that was confirmed by electron microscopy. Furthermore, the lack of CD90 and CD13 staining in a wide range of melanocytic lesions suggests specificity of these markers for spindle cell melanoma.
Appl Immunohistochem Mol Morphol 2003 Dec
PMID:New phenotypical and ultrastructural findings in spindle cell (desmoplastic/neurotropic) melanoma. 1466 57

Earthworm innate immunity depends upon small and large leukocytes (coelomocytes) that synthesize and secrete humoral antimicrobial molecules (e.g. lysenin, fetidin, eiseniapore, coelomic cytolytic factor [CCF]; Lumbricin I). Small coelomocytes (cytotoxic) are positive (CD11a, CD45RA, CD45RO, CDw49b, CD54, beta(2)-m and Thy-1 [CD90]; CD24; TNF-alpha) but negative using other mammalian markers. Large coelomocytes (phagocytic) are uniformly negative. Specific earthworm anti-EFCC 1, 2, 3, 4 mAbs are negative for Drosophila melanogaster hemocytes and mammalian cells but positive those of earthworms. Coelomocytes contain several lysosomal enzymes involved in phagocytosis and a pattern recognition molecule (CCF) that may trigger the prophenoloxidase cascade a crucial innate immune response. Earthworms and other invertebrates possess natural, non-specific, non-clonal, and non-anticipatory immune response governed by germ line genes. Toll and Toll-like receptor signaling is essential for phagocytosis and antimicrobial peptide synthesis and secretion in insects and vertebrates but has not yet been shown to be essential in earthworm innate responses.
Mol Immunol 2005 May
PMID:Anticipating innate immunity without a Toll. 1582 85

The piwi family genes are highly conserved during evolution and play essential roles in stem cell self-renewal, gametogenesis, and RNA interference in diverse organisms ranging from Arabidopsis to human. Piwil2, known also as Mili gene, is one of three mouse homologues of piwi. Piwil2 was found in germ cells of adult testis, suggesting that this gene functions in spermatogonial stem cell self-renewal. In order to find molecular mechanisms underlying stem cell activity mediated by Piwil2 gene, an in vitro gain of function cell culture model was established. Messenger RNAs isolated from cells expressing Piwil2 and mRNAs isolated from cells without Piwil2 expression were compared using a stem cell array technique. It was shown that Piwil2 modulates expression of stem cell specific genes, including platelet-derived growth factor receptor, beta polypeptide (Pdgfrb), solute carrier family 2 member 1 (Slc2a1), gap junction membrane channel protein alpha 7 (Gja7), and spermatogonial cell surface markers Thy-1 (CD90), integrin alpha 6 (Itga6), CD9, and spermatogonia specific markers heat shock protein 90 alpha (Hsp90a), and stimulated by retinoic acid gene 8 (Stra8). These molecules play essential role in stem cells proliferation (Pdgfrb), energy metabolism (Slc2a1), cell adhesion, cell-cell interaction (Itga6, Gja7, Thy-1, and CD9), and germ cell differentiation (Stra8). The expression of these markers in spermatogonial stem cells and other nongerminal stem cells suggests that these cells share elements of common molecular machinery with stem cells in other tissues which are modulated by stem cell protein Piwil2.
Mol Reprod Dev 2006 Feb
PMID:Stem cell protein Piwil2 modulates expression of murine spermatogonial stem cell expressed genes. 1626 12

Adult male Wistar rats were subjected to propranolol (P, 0.40 mg/100 g/day) or saline (S) administration (controls) over 14 days. The expression of major differentiation molecules on thymocytes and Thy-1 (CD90) molecules, which are shown to adjust thymocyte sensitivity to TCRalphabeta signaling, was studied. In addition, the sensitivity of thymocytes to induction of apoptosis and concanavalin A (Con A) signaling was estimated. The thymocytes from P-treated (PT) rats exhibited an increased sensitivity to induction of apoptosis, as well as to Con A stimulation. Furthermore, P treatment produced changes in the distribution of thymocyte subsets suggesting that more cells passed positive selection and further differentiated into mature CD4+ or CD8+ single positive (SP) TCRalphabeta(high) cells. These changes may, at least partly, be related to the markedly increased density of Thy-1 surface expression on TCRalphabeta(low) thymocytes from these rats. The increased frequency of cells expressing the CD4+25+ phenotype, which has been shown to be characteristic for regulatory cells in the thymus, may also indicate alterations in thymocyte selection following P treatment. Inasmuch as positive and negative selections play an important role in continuously reshaping the T-cell repertoire and maintaining tolerance, the hereby presented study suggests that pharmacological manipulations with beta-AR signaling, or chemically evoked alterations in catecholamine release, may interfere with the regulation of thymocyte selection, and consequently with the immune response.
Mol Cell Biochem 2006 Apr
PMID:Characterization of thymocyte phenotypic alterations induced by long-lasting beta-adrenoceptor blockade in vivo and its effects on thymocyte proliferation and apoptosis. 1647 76

The differentiation of B lymphocytes in the bone marrow is guided by the surrounding microenvironment determined by cytokines, adhesion molecules, and the extracellular matrix. These microenvironmental factors are mainly provided by stromal cells. In this paper, we report the identification of a VCAM-1-positive stromal cell population by flow cytometry. This population showed the expression of cell surface markers known to be present on stromal cells (CD10, CD13, CD90, CD105) and had a fibroblastoid phenotype in vitro. Single cell RT-PCR analysis of its cytokine expression pattern revealed transcripts for haematopoietic cytokines important for either the early B lymphopoiesis like flt3L or the survival of long-lived plasma cells like BAFF or both processes like SDF-1. Whereas SDF-1 transcripts were detectable in all VCAM-1-positive cells, flt3L and BAFF were only expressed by some cells suggesting the putative existence of different subpopulations with distinct functional properties. In summary, the VCAM-1-positive cell population seems to be a candidate stromal cell population supporting either developing B cells and/or long-lived plasma cells in human bone marrow.
Mol Immunol 2007 Mar
PMID:VCAM-1-positive stromal cells from human bone marrow producing cytokines for B lineage progenitors and for plasma cells: SDF-1, flt3L, and BAFF. 1706 79

Bone marrow-derived mesenchymal stem cells consist of a developmentally heterogeneous population of cells obtained from colony forming progenitors. As these colonies express the alpha-1 integrin (CD49a), here we single-cell FACS sorted CD49a+ cells from bone marrow in order to create clones and then compared their colony forming efficiency and multilineage differentiation capacity to the unsorted cells. Following selection, 40% of the sorted CD49a+ cells formed colonies, whereas parental cells failed to form colonies following limited dilution plating at 1 cell/well. Following ex vivo expansion, clones shared a similar morphology to the parental cell line, and also demonstrated enhanced proliferation. Further analysis by flow cytometry using a panel of multilineage markers demonstrated that the CD49a+ clones had enhanced expression of CD90 and CD105 compared to unsorted cells. Culturing cells in adipogenic, osteogenic or chondrogenic medium for 7, 10 and 15 days respectively and then analysing them by quantitative PCR demonstrated that CD49a+ clones readily underwent multlineage differentiation into fat, bone and cartilage compared to unsorted cells. These results thus support the use of CD49a selection for the enrichment of mesenchymal stem cells, and describes a strategy for selecting the most multipotential cells from a heterogeneous pool of bone marrow mononuclear stem cells.
J Mol Histol 2007 Oct
PMID:Selection using the alpha-1 integrin (CD49a) enhances the multipotentiality of the mesenchymal stem cell population from heterogeneous bone marrow stromal cells. 1769 77

The study of fibroblast-like synoviocytes (FLS) has yielded important insights into the pathogenic mechanisms of rheumatoid arthritis. FLS can be cultured from synovial tissue obtained at joint replacement surgery, synovectomy, or synovial biopsy. After collagenase digestion, adherent cells consist mainly of synovial fibroblasts and synovial macrophages. Proliferating FLS are enriched by repeated passage and comprise >95% of cells by passage 3. Because of cell senescence, use of FLS lines after passage 9 is generally not recommended. FLS in culture have a distinct phenotype with regard to morphology, ultrastructure, surface phenotype, and function. Surface markers that can be used to characterize FLS include positive staining for VCAM-1, CD44, CD55, CD90 (Thy-1), and cadherin-11, coupled with the absence of macrophage markers such as CD14 or CD68.
Methods Mol Med 2007
PMID:Acquisition, culture, and phenotyping of synovial fibroblasts. 1795 72

Bone marrow (BM) mesenchymal stem cells (MSCs) are non-hematopoietic cells capable of generating colonies of plastic-adherent marrow mesenchymal cells, each derived from a single cell termed a colony-forming unit fibroblasts (CFU-Fs). In addition to their role in establishing the marrow microenvironment, these cells have been shown to differentiate into several types of mesenchymal and non-mesenchymal lineages. Because of their multipotency, MSCs represent an attractive cellular source in the promising field of cellular therapy. In this chapter, we will focus on culture conditions for human BM MSC expansion and CFU-F assays. We also describe the methodologies to analyze the primary cultures obtained, both at the phenotypic and at the functional levels. Phenotypically, MSCs can be defined with a minimal set of markers as CD31-, CD34-, and CD45-negative cells and CD13-, CD29-, CD73-, CD90-, CD105-, and CD166-positive cells. Functionally, we describe the culture conditions (specific media and cellular preparations) for in vitro differentiation of MSCs into the adipogenic, osteogenic, and chondrogenic lineages. The corresponding colorimetric assays (oil red O, Von Kossa and alizarin red S, and safranin O and alcian blue stains, respectively) are also described.
Methods Mol Med 2007
PMID:Culture and characterization of human bone marrow mesenchymal stem cells. 1808 3

The purpose of this study was to investigate the expression of different CD44 and hyaluronan synthase isoforms in cartilage, their alterations during the chondrocyte dedifferentiation process in monolayer culture and during the redifferentiation process on 3D scaffolds. Chondrocytes isolated from human articular cartilage were cultured as a monolayer for up to 36 days and were seeded on two different 3D scaffolds (HYAFF 11 and Bio-Gide). Expression levels of CD44s, CD44-lt, CD44-st, HAS1, HAS2, HAS3 and UDPGD were determined by real-time RT-PCR at different time points. At the protein level CD44 and CD90 were analyzed by flow cytometry. HAS2 was found to be the predominantly expressed hyaluronan synthase in chondrocytes and was not subjected to any regulation during the dedifferentiation process. CD44s, CD44-lt, CD44-st and UDPGD, however, were upregulated immediately after cell isolation. In addition, a high cell density was found to significantly increase CD44-st and CD44-lt expression. Redifferentiation on 3D scaffolds reversed the increase of the CD44 expression. Our data point out that CD44 expression does not correlate with matrix assembly in chondrocytes and that CD44 has a regulatory function in chondrocytes, not necessarily on differentiation, but probably on proliferation.
Int J Mol Med 2009 Feb
PMID:Alterations in CD44 isoforms and HAS expression in human articular chondrocytes during the de- and re-differentiation processes. 1914 50


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