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1.
Based on the capacity to transfer alpha-L-fucose onto type-1 and type-2 synthetic blood group H and sialylated acceptors, a comparison of the alpha-3-fucosyltransferase activities of different human tissues is shown. Three distinct acceptor specificity patterns are described: (I) myeloid alpha-3-fucosyltransferase pattern, in which leukocytes and brain enzymes transfer fucose actively onto H type-2 acceptor and poorly onto sialylated N-acetyllactosamine: (II) plasma alpha-3-fucosyltransferase (EC 2.4.1.152), in which plasma and hepatocyte enzymes transfer, in addition, onto the sialylated N-acetyllactosamine; (III) Lewis alpha-3 4-fucosyltransferase (EC 2.4.1.65), in which gall-bladder kidney and milk enzymes transfer, in addition, onto type-1 acceptors. The small amount (less than 10%) of alpha-3-fucosyltransferase activity found in the plasma of an alpha-3-fucosyltransferase-deficient individual had a myeloid-type acceptor pattern, suggesting that this small proportion of the plasma enzyme is derived from leukocytes. In addition to the three acceptor specificity patterns, these enzyme activities can be differentiated by their optimum pH: 8.0-8.7 for the enzymes from myeloid cells and brain. 7.2-8.0 for liver enzymes and 6.0-7.2 for gallbladder enzymes. Milk samples had two alpha-3-fucosyltransferase activities, the Lewis or alpha-3/4-fucosyltransferase under control of the Lewis gene and an alpha-3-fucosyltransferase with plasma acceptor pattern which was independent of the control of the Lewis gene. The apparent affinity for GDP-fucose of the myeloid-like enzyme was weaker than those of the plasma and Lewis-like enzymes. The apparent affinities for H type 2 and sialylated N-acetyllactosamine were stronger for exocrine secretions as compared to the plasma and myeloid enzymes. The plasma type of alpha-3-fucosyltransferase activity was more sensitive to N-ethylmaleimide and heat inactivation than the samples with myeloid-like alpha-3-fucosyltransferase activity.  相似文献   

2.
Sera from H normal, secretors and nonsecretors (H/-, Se/- and H/-, se/se), as well as from H-deficient secretors (h/h, Se/- or Bombay secretors) contain enzyme(s) for the transfer of L-fucose in the alpha-configuration to the 2-position of suitable beta-D-galactopyranosyl units. Sera from H-deficient nonsecretors (h/h, se/se; i.e., Bombay nonsecretors) are devoid of such beta-D-Gal alpha-2-L-fucosyltransferase(s). In order to study these enzymes, a comparison was made of the kinetic properties of the enzymes present in the sera of H-normal nonsecretors (H/-, se/se) with those of H-deficient secretors (h/h, Se/se) with those of H-deficient secretors (h/h, Se/-). These studies revealed a clear difference between the two sources of enzyme: (1) the apparent Km for GDP-fucose was four times lower with the H-normal nonsecretor serum (0.008 mM) than with the H-deficient secretor serum (0.028 mM); (2) acceptors with a type 1 or type 3 chain proved to be better than acceptors with a type 2 chain or than phenyl-beta-D-galactopyranoside for the enzyme present in the serum of H-deficient secretor individuals. Indeed, the synthetic type 2 compound, betaDGal (1-->4)-3-deoxy-beta-DGlcNAc-1-OCH3, which cannot act as an acceptor of beta DGlcNAc alpha-3/4-L-fucosyltransferases, remained unchanged in the serum of an H-deficient secretor but was a good acceptor in the serum of an H-normal nonsecretor, and (3) the alpha-2-L fucosyltransferease activity of the H-deficient secretor serum was more sensitive to heat inactivation than that of the H-normal nonsecretor serum (t1/2 at 46 degrees C were 10 min and 75 min, respectively). These results show that at least two distinct alpha-2-L-fucosyltransferases are present in human serum. It is concluded that the enzymatic activity found in the H-deficient secretor serum (h/h, Se/-) could be the product of the Se gene and the enzymatic activity found in the H-normal nonsecretor serum (H/-, se/se) could be the product of the H gene. This conclusion correlates well with the finding that H and Se genes are closely linked and might have derived by gene duplication in the course of evolution.  相似文献   

3.
A radioimmunoassay specific for the H type 1 antigenic determinant demonstrated that the H type 1 antigen is under the strict control of the Se gene in both serum and saliva. Similar amounts of H type 1 antigenic determinants were found in saliva from Se/-, le/le donors and in saliva from Se/-, Le/- donors. However, sera from Se/-, le/le donors were about 100 times more efficient in inhibiting the H type 1 assay than were sera from Se/-, Le/- donors. A radioimmunoassay, based on the binding of Ulex europaeus with the H type 2 antigenic determinant, showed that all the H type 2 antigen in saliva is under the control of the Se gene, while only one-third of the H type 2 antigen present in serum is under the control of this gene. The remaining two-thirds of H type 2 antigen in sera is independent of the ABH secretor status of the donor. The amount of H type 2 antigen in both serum and saliva is independent of the Le gene. These results are compatible with the existence of two alpha (1 leads to 2) fucosyl-transferases but suggest that the enzyme of epithelial origin, coded by the Se gene, should be able to transform both type 1 and type 2 natural substrates, while the enzyme of mesodermic origin, coded by the H gene, would work preferentially on the natural type 2 substrates.  相似文献   

4.
Lewis b (Leb) antigens are gradiently expressed from the proximal to the distal colon, i.e., they are abundantly expressed in the proximal colon, but only faintly in the distal colon. In the distal colon, they begin to increase at the adenoma stage of cancer development and then increase with cancer progression. We aimed to clarify the molecular basis of Leb antigen expression in correlation with the expression of other type I Lewis antigens, such as Lewis a (Lea) and sialylated Lewis a (sLea), in colon cancer cells. Considering the Se genotype and the relative activities of the H and Se enzymes, the amounts of Leb antigens were proved to be determined by both the H and Se enzymes in noncancerous and cancerous colon tissues. But the Se enzyme made a much greater contribution to determining the Lebamounts than the H enzyme. In noncancerous colons, the Se enzyme were gradiently expressed in good correlation with the Leb expression, while the H enzyme was constantly expressed throughout the whole colon. In distal colon cancers, the H and Se enzymes were both significantly upregulated in comparison with in adjacent noncancerous tissues. In proximal colon cancers, expression of the H enzyme alone was highly augmented. The augmented expression of Leb antigens in distal colon cancers is caused mainly by upregulation of the Se enzyme and partly by the H enzymes, while it is caused by upregulation of the H enzyme alone in proximal colon cancers. The Se gene dosage profoundly influences the amounts of the Leb, Lea, and sLea antigens in whole colon tissues, regardless of whether they are noncancerous or cancerous tissues. It suggests that the Se enzyme competes with alpha2,3 sialyltransferase(s) and the Le enzyme for the type I acceptor substrates.  相似文献   

5.
Monoclonal rat antibodies were prepared against glycoproteins isolated from murine teratocarcinoma OTT6050 by affinity chromatography on Ricinus communis agglutinin (RCA). These antibodies defined three distinct groups of antigens (OR antigens) commonly expressed in teratocarcinoma cells and in restricted sites of the kidney. OR 17 antigen was a new glycoprotein antigen and the biochemical properties were different from any membrane glycoprotiens or matrix glycoproteins so far described in teratocarcinoma cells. In the kidney, the antigen was found in the glomerular basement membrane, and to lesser extent in the endothelium of the glomerulus and blood vessels. On the other hand, OR 8 antigen corresponded to "brushin" defined by conventional antibodies, while OR 4 and 19 antigens were carbohydrate antigens resembling "TC antigen". OR 8 antigen was detected in the tubular brush border and the epithelium of Bowman's capsule. OR 4 antigen was present in the collecting tubules and the thin loop of Henle. Although OR 19 antigen showed distribution similar to OR 4 antigen, there were genetic differences in the expression of the former antigen. All of the antigens were present in early postimplantation embryos of the mouse, notably in the visceral endoderm. These antigens are interesting subjects to study the mechanism of differentiation-dependent control of gene expression, since antigenic distribution is specialized as the result of differentiation.  相似文献   

6.
The occurrence of GDP-L-fucose:N-acetyl-β-D-glucosaminyl α-3-L-fucosyltransferase activity in human saliva was independent of Lewis blood group and ABH secretor status except insofar as the mean level of activity was higher in saliva from individuals with an Le gene than in those whose red cells and saliva grouped as Le(a-b-). In contrast GDP-L-fucose:D-glucose α-3-L-fucosyltransferase activity was detectable in saliva from all Le(a+b-) and Le(a-b+) individuals but was absent from the salivas of Le(a-b-) donors. Isoelectric focusing experiments supported the inference that there are two distinct α-3-L-fucosyltransferase activities in saliva. Both enzymes appear to catalyse the transfer of L-fucose to the C-3 position of N-acetyl-β-D-glucosamine but only the transferase dependent upon the expression of the Le gene has the capacity to transfer L-fucose to the C-3 position of D-glucose.  相似文献   

7.
In the vertebrate embryo, development of the excretory system is characterized by the successive formation of three distinct kidneys: the pronephros, mesonephros, and metanephros. While tubulogenesis in the metanephric kidney is critically dependent on the signaling molecule Wnt-4, it is unknown whether Wnt signaling is equally required for the formation of renal epithelia in the other embryonic kidney forms. We therefore investigated the expression of Wnt genes during the pronephric kidney development in Xenopus. Wnt4 was found to be associated with developing pronephric tubules, but was absent from the pronephric duct. Onset of pronephric Wnt-4 expression coincided with mesenchyme-to-epithelium transformation. To investigate Wnt-4 gene function, we performed gain- and loss-of-function experiments. Misexpression of Wnt4 in the intermediate and lateral mesoderm caused abnormal morphogenesis of the pronephric tubules, but was not sufficient to initiate ectopic tubule formation. We used a morpholino antisense oligonucleotide-based gene knockdown strategy to disrupt Wnt-4 gene function. Xenopus embryos injected with antisense Wnt-4 morpholinos developed normally, but marker gene and morphological analysis revealed a complete absence of pronephric tubules. Pronephric duct development was largely unaffected, indicating that ductogenesis may occur normally in the absence of pronephric tubules. Our results show that, as in the metanephric kidney, Wnt-4 is critically required for tubulogenesis in the pronephric kidney, indicating that a common, evolutionary conserved gene regulatory network may control tubulogenesis in different vertebrate excretory organs.  相似文献   

8.
The reactivity of a panel of monoclonal antibodies (MAb) produced against non-T, non-B acute lymphoblastic leukemia cells was investigated by immunoperoxidase staining of sections of normal human kidney. The antigens of kidney reactive with the MAb were isolated by immunoaffinity chromatography and were purified further by immunoprecipitation. Two MAb, 44D7 and 44H9, reacted with determinants found exclusively on the basolateral membranes of proximal convoluted tubules. The 44D7 antigen isolated from kidney was biochemically similar to that isolated from leukemic cells. It was resolved as a multimeric complex with an apparent m.w. of 120,000 when analyzed by SDS-PAGE under nonreducing conditions. The 44H9 antigen has not yet been purified from kidney. MAb 50B4 reacted with components of the interstitium and with the mesangium of glomeruli. It immunoprecipitated a polypeptide chain of apparent m.w. 85,000, similar to that of the 50B4 antigen isolated from leukemic cells. MAb 44G4 also reacted with the mesangium of glomeruli and with the interstitium of the kidney. However, the endothelium of glomerular capillaries and of interstitial blood vessels has also reacted with MAb 44G4. The kidney antigen recognized by MAb 44G4 was characterized as a major polypeptide band, 95,000 m.w. (reduced) and 125,000 m.w. (nonreduced), a subunit structure analogous to the 44G4 antigen isolated from leukemic cells. MAb 44E3 reacted with all cellular elements of glomeruli, tubules, blood vessels, and interstitium. Two polypeptide chains of apparent m.w. 94,000 and 90,000 were immunoprecipitated from kidney by MAb 44E3, while a single polypeptide chain of 94,000 m.w. was precipitated from leukemic cells. Our results describe five new antigens with distinctive cellular distributions within kidney.  相似文献   

9.
Summary Epithelia frequently express blood group antigens and these are often perturbed in neoplasia. This study has characterized the range of expression of ABH and Lewis terminal structures and the Ii backbone chains in the normal human cervix by semiquantitative immunohistochemistry. Effects of the secretor gene were defined by determination of salivary secretor status. Modifications of blood group antigen expression in cervical adenocarcinoma were also addressed.Normal cervical squamous and glandular epithelia showed a range of expression of the antigens studied. Lewis-gene-negative cases showed no expression of Lewis antigens. Secretor status had no effect on ABH expression in squamous epithelium, but it did have a marked effect on ABH expression in glands and on Leb expression in both squamous and glandular epithelia. Patterns of expression of i chains in squamous epithelium suggest that these may be the carriers of ABH and Lewis antigens in a proportion of cases. Distinct patterns of expression were seen in glandular tubal metaplasia and in endothelium.Adenocarcinomas showed topographical rather than quantitative changes in blood group antigen expression with more extensive luminal expression of ABH, Lewis and Ii structures than that seen in normal glands. This change is distinct from those usually associated with malignancy.  相似文献   

10.
We investigated the subcellular localization of ABH antigens in human submandibular, sublingual, and buccal glands by applying a post-embedding immunogold method using monoclonal antibodies specific for A, B, and H antigens. In most glands the immunoreactivity was usually restricted to mucous cells, in which only secretory granules and sometimes Golgi cisternae were specifically labeled. A and B antigens were demonstrated only in the glands of type A, B, and AB subjects, while H antigen was visualized in glands from individuals of all blood types. Moreover, differences were observed in the relative distribution of ABH antigens, depending on the type of gland.  相似文献   

11.
Histo-blood group ABH antigens are widely distributed in human tissues. The epitopes of ABH antigens are carried by at least four different peripheral core isotypes of internal carbohydrate backbones (type 1-4). Each type of ABH antigen is expressed tissue specifically, and aberrant expression of ABH antigens is often observed during oncogenesis. We immunohistochemically examined the expression of A type 3 antigens in wounded and diseased skin tissues (A and AB blood groups). In uninjured skin, the expression of A type 3 antigens was restricted to the eccrine sweat gland. In addition to the sweat glands, A type 3 antigens were found in vascular endothelial cells of the wound sites. The extent of A type 3 antigens expression related to postinfliction intervals. A significantly higher expression rate of A type 3 antigens in endothelial cells was also observed in diseased skin, suggesting that inflammation might induce A type 3 antigen expression in endothelial cells. Double-color immunofluorescence staining of the specimens showed that von Willebrand factor (vWF) was a core-protein of A type 3 determinants aberrantly expressed in endothelial cells in inflamed tissues, suggesting that aberrant expression of A type 3 antigens is involved in stabilization of vWF in inflammation.  相似文献   

12.
Forty-two H-deficient individuals (lacking H antigen on erythrocytes) with anti-H in their sera were found on Reunion Island. A, B, and AB Bombay subjects had small but detectable amounts of A and/or B antigens on erythrocytes. All the H-deficient phenotypes tested were nonsecretors of ABH in their saliva, and one-third were Lewis negative. Fifty-three of the 108 (49%) unaffected members in the 14 Bombay pedigrees analyzed were se/se, showing that the families were selected for the nonsecretor trait, and suggesting that the Bombay probands used to select the families have se/se genotype. In accordance with this concept, all the children from Bombay nonsecretor x unaffected nonsecretor matings were se/se. Segregation of H and Se is compatible with the genetic model proposing that Se and H are closely linked structural genes, and the analysis of the present and previously published Bombay pedigrees strongly supports this model.  相似文献   

13.
Expression of type 1 and type 2 chain Lewis antigens was studied in 32 rectal adenocarcinoma specimens; the results were correlated with the patients' Lewis phenotype and secretor status. In addition, the pattern of expression of these antigens was analyzed in adjacent and distant normal mucosa. We used an indirect immunofluorescence technique with p-phenylenediamine counterstaining (Oriol technique) and a panel of monoclonal antibodies directed against the different antigenic specificities. Normal distal colonic mucosa only expresses monofucosylated structures (Lea and X) arising from activity of the alpha 1-3,4-fucosyltransferase coded by the Le gene. Rectal adenocarcinomas also show Lea and X, but also reexpress blood group antigens ABH and exhibit difucosylated determinants (Leb and Y). The accumulation of mono- and difucosylated type 2 chain in neoplastic processes, independently of the Le and Se genes, could be due to the enzymes coded by reactivation of the H and X genes. Blood group antigens form a complex signal code, genetically regulated, which intervenes in differentiation, growth and cellular recognition processes, and which may undergo important modifications during malignant transformation. These alterations could be useful in the diagnosis and prognosis of some types of carcinoma.  相似文献   

14.
The distribution of blood group antigens ABH in submandibular glands was studied at light and electron microscopy levels by applying ImmunoGold Silver Staining (IGSS) and post-embedding ImmunoGold (IGS) methods, respectively. In IGSS treated samples, a cytoplasmic and a surface form of antigen localization were discernible in the glandular parenchyma. The former was restricted to most mucous cells and to scattered serous cells: A and B antigens were demonstrated in mucous cells of A and B type glands, while H antigen appeared in most mucous and occasional serous elements regardless of the blood type of donors. The latter appeared as a strong H reactivity on cell surfaces of serous acini and ducts regardless of the patient blood type. The IGS method was applied both on non-osmicated samples embedded in LR White resin and on osmicated, Epon embedded samples. In non-osmicated tissues, antigen labelling was revealed in secretory granules and cell surfaces. Positive secretory granules were found in most mucous cells and occasional serous, intercalated, and striated duct cells. A and B antigens weakly reacted in mucous cells of A and B type glands, respectively, while strong H reactivity was seen in mucous, serous, intercalated and striated duct cells of glands of all types. Surfaces labelled with H antigen were found on both lumenal and basolateral membranes of striated ducts in glands of all types. IGS method applied on osmicated, Epon embedded samples, selectively revealed blood group antigens in secretory granules of serous cells but not in the apical vesicles of striated ductal cells. Cell surfaces were completely unreactive.  相似文献   

15.
The ability of rabbit hemorrhagic disease virus to agglutinate human erythrocytes and to attach to rabbit epithelial cells of the upper respiratory and digestive tracts was shown to depend on the presence of ABH blood group antigens. Indeed, agglutination was inhibited by saliva from secretor individuals but not from nonsecretors, the latter being devoid of H antigen. In addition, erythrocytes of the rare Bombay phenotype, which completely lack ABH antigens, were not agglutinated. Native viral particles from extracts of infected rabbit liver as well as virus-like particles from the recombinant virus capsid protein specifically bound to synthetic A and H type 2 blood group oligosaccharides. Both types of particles could attach to adult rabbit epithelial cells of the upper respiratory and digestive tracts. This binding paralleled that of anti-H type 2 blood group reagents and was inhibited by the H type 2-specific lectin UEA-I and polyacrylamide-conjugated H type 2 trisaccharide. Young rabbit tissues were almost devoid of A and H type 2 antigens, and only very weak binding of virus particles could be obtained on these tissues.  相似文献   

16.
Based on the genetic model proposing thatH andSe are two structural genes, we predicted that the red cell H-deficient, salivary ABH secretor phenotype should be found on Reunion island, where a large series of H-deficient non-secretor families have been previously described. Two such Reunion individuals are now reported. POU [Ah, Le(a–b+), secretor of A, H, Lea and Leb in saliva] and SOU [Oh, Le(a–b+), secretor of H, Lea and Leb in saliva]. Both are devoid of H -2-fucosyltransferase activity in serum. In addition, the preparation of total non-acid glycosphingolipids from plasma and red cells of POU revealed the type 1ALeb heptaglycosylceramide and small amounts of the monofucosylated type 1 A hexaglycosylceramide. Both glycolipids possess an H structure probably synthesised by the product of theSe gene. No other blood group A glycolipids, with types 2, 3 or 4 chains, normally present in the presence of the product of theH gene, were found on red cells or plasma of POU.TheH,Se andLe genetic control of the expression of ABH and related antigens in different tissue structures of the skin is described in 54 H-normal individuals of known ABO, secretor and Lewis phenotypes; in one red cell H-deficient salivary secretor (SOU); and in one H-deficient non-secretor (FRA). Sweat glands express ABH under the control of theSe gene. Sweat ducts express ABH under the control of bothH andSe genes and Lewis antigens under the control ofLe and bothH andSe genes. Epidermis, vascular endothelium and red cells express ABH under the control of theH gene. The products ofH andSe genes are usually expressed in different cells. However, the results illustrate that in some structures, like the epithelial cells of sweat ducts, both the products ofH andSe genes can contribute to the synthesis of the same Leb structure.  相似文献   

17.
Using a post-embedding immunogold labeling procedure, we found that monoclonal antibody against A (MAb-A) or B antigen (MAb-B) reacted with nuclear heterochromatin regions, as well as secretory granules, in mucous cells of human cervical glands. Systematic and critical observation of specimens from 24 individuals of different blood groups revealed that the labeling pattern with MAb with strictly dependent on the blood group (A,B, or O) of the donors, i.e., MAb-A reacted with the heterochromatin from blood group A and AB but not with B and O individuals. Labeling with MAb-B was also specific for the heterochromatin from blood group B donors. On the other hand, MAb against H antigen did not react with the heterochromatin from any individuals examined, despite the fact that H antigens were detected by the MAb in secretory granules. Such specific reactions provide evidence that certain types of blood group-related antigens exist in the nuclear heterochromatin in mucous cells of human cervical glands. In contrast to the secretory granules in which ABH antigens were recognized by blood group-specific lectin, heterochromatin regions had little or no affinity for these lectins. Furthermore, the secretory status of individuals affected the staining intensity with MAb in secretory granules but not in the heterochromatin. These results suggest that the blood group substances found in the heterochromatin may have different molecular properties from those in the secretory granules, although both have the same determinant structures of ABH antigens.  相似文献   

18.
In 1980 blood and saliva samples were taken from Spanish students of the University of Madrid. Red cells were analysed for A1B2BO and Lewis blood groups. Saliva samples were tested to detect the specific group substances ABH, Lea and Leb. A slightly higher frequency of the "le" gene (0.419) was found in our sample as compared to other Spanish samples. The phenotype frequencies of ABH secretors (77.2%) and non-secretors (22.8%) are in the range of other European populations. The levels of A and B antigens of individuals belonging to these blood groups were similar, whereas the average titration of the H substance showed the relation O greater than A2 greater than A1 greater than A1B greater than B. Analysis of variance proved this heterogeneity to be statistically significant. The amount of Lea substance in non-secretors was higher than in secretors. This shows again that the ABH secretor status has some influence on the quantity of this antigen. The average titration of the Leb substance in secretors was higher than that of Lea in individuals belonging to O, A and AB blood groups, but not in those with blood group B.  相似文献   

19.
20.
The Lewis blood group system among Chinese in Taiwan.   总被引:2,自引:0,他引:2  
The nonsecretor gene se is absent (or very rare) among Chinese in Taiwan and the previously reported Le(a+b-) phenotype in this population is in fact Le(a+b+) as proven by the presence of small amounts of Leb antigen on red blood cells. Salivary ABH substances in this phenotype are usually (although not always) markedly reduced. The Chinese Le(a+b+) phenotype is postulated to be the result of a weak secretor gene Se omega. Although the Le(a+b+) phenotype is very rare in Caucasians, it has a frequency of 25% in Chinese. All Le(a-b-) Chinese are ABH secretors and have varying amounts of Lea and/or Leb substances in saliva.  相似文献   

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