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• W2094693609 abstract "Alterations in cell to cell adhesion are necessary to enable the type of cell movements that are associated with epithelial wound healing and malignant invasion. Several studies of transformed cells have related epithelial cell movement to changes in the cell surface expression of the carbohydrate structures represented by the ABO blood group antigens and, in particular, by Lewis antigens and their biosynthetic precursors. To study further the relationship between cell surface carbohydrates and keratinocyte cell movement, experimental wounds were created in human oral mucosa and examined by immunohistochemical methods for their expression of selected cytokeratins (K5, K16, K19), basement membrane components (laminin α5 and γ2-chains, BP180, collagen IV and collagen VII), and blood group antigen precursor structures Lex, sialosyl-Lex, Ley, H antigen, N-acetyllactosamine, and sialosyl-T antigen. The changes induced by wounding in the expression of collagen IV, laminin γ2-chain (laminin-5), and laminin α5-chain were similar to those found in skin wounds and served to define the region of epithelial movement. This region was found to show a marked increase in staining for both Lewis antigen Y (Ley) and H blood group antigen, and decreased staining of Lex, thus indicating an upregulation in wounded epithelium of the fucosyltransferases responsible for the synthesis of the H antigen. The changes in carbohydrate expression extended beyond the wound margin into the nonwounded epithelium, a pattern of expression similar to K16, which was also strongly upregulated in both the outgrowth and the adjacent nonwounded epithelium. These findings provide further support for an influence of such carbohydrate structures on the migratory behavior of epithelial cells. Alterations in cell to cell adhesion are necessary to enable the type of cell movements that are associated with epithelial wound healing and malignant invasion. Several studies of transformed cells have related epithelial cell movement to changes in the cell surface expression of the carbohydrate structures represented by the ABO blood group antigens and, in particular, by Lewis antigens and their biosynthetic precursors. To study further the relationship between cell surface carbohydrates and keratinocyte cell movement, experimental wounds were created in human oral mucosa and examined by immunohistochemical methods for their expression of selected cytokeratins (K5, K16, K19), basement membrane components (laminin α5 and γ2-chains, BP180, collagen IV and collagen VII), and blood group antigen precursor structures Lex, sialosyl-Lex, Ley, H antigen, N-acetyllactosamine, and sialosyl-T antigen. The changes induced by wounding in the expression of collagen IV, laminin γ2-chain (laminin-5), and laminin α5-chain were similar to those found in skin wounds and served to define the region of epithelial movement. This region was found to show a marked increase in staining for both Lewis antigen Y (Ley) and H blood group antigen, and decreased staining of Lex, thus indicating an upregulation in wounded epithelium of the fucosyltransferases responsible for the synthesis of the H antigen. The changes in carbohydrate expression extended beyond the wound margin into the nonwounded epithelium, a pattern of expression similar to K16, which was also strongly upregulated in both the outgrowth and the adjacent nonwounded epithelium. These findings provide further support for an influence of such carbohydrate structures on the migratory behavior of epithelial cells. Epithelial cells are not usually motile and alterations of the normal epithelial phenotype, particularly those influencing patterns of cell adhesion, may be required for the various types of cell movements that are associated with wound healing, malignant transformation, and metastasis (Kohn and Liotta, 1995Kohn E.C. Liotta L.A. Molecular insights into cancer invasion: strategies for prevention and intervention.Cancer Res. 1995; 55: 1856-1862PubMed Google Scholar). It is generally agreed that an alteration in cell to substrate adhesion is necessary for the migration of epithelial cells onto or into deep connective tissues, and several studies have shown functionally correlated changes in the expression of matrix molecules and integrin-type cell surface receptors (Gailit and Clark, 1994Gailit J. Clark R.A.F. Wound repair in the context of extracellular matrix.Curr Opin Cell Biol. 1994; 6: 717-725Crossref PubMed Scopus (364) Google Scholar). Both reparative and invasive growth of squamous epithelium, however, may also require altered cell to cell adhesion. The normal differentiation process of oral mucosal keratinocytes is associated with expression of a precise sequence of precursor and terminal carbohydrate structures at the cell surface (Dabelsteen et al., 1991Dabelsteen E. Mandel U. Clausen H. Cell surface carbohydrates are markers of differentiation in human oral epithelium.CRC Crit Rev Oral Biol Med. 1991; 2: 493-507PubMed Google Scholar). The functional relationship of these molecules to epithelial cell movement remains uncertain but some cell surface carbohydrates can act as ligands for selectins that form a group of adhesion molecules containing a lectin-like carbohydrate binding domain (Lowe et al., 1990Lowe J.B. Stoolman L.M. Nair R.P. Larsen R.D. Berhend T.L. Marks R.M. ELAM-1-dependent cell adhesion to vascular endothelium determined by a transfected human fucosyltransferase cDNA.Cell. 1990; 63: 475-484Abstract Full Text PDF PubMed Scopus (656) Google Scholar;Berg et al., 1991Berg E.L. Robinson M.K. Mansson O. Butcher E.C. Magnani J.I. A carbohydrate domain common to both sialyl Lea and sialyl Lex is recognized by the endothelial cell leukocyte adhesion molecule ELAM-1.J Biol Chem. 1991; 266: 14869-14872Abstract Full Text PDF PubMed Google Scholar), and changes in epithelial cell surface carbohydrates may in certain situations be required for cell motility regulation (Miyake and Hakomori, 1991Miyake M. Hakomori S. A specific cell surface glycoconjugate controlling cell motility: evidence by functional monoclonal antibodies that inhibit cell motility and tumor cell metastasis.Biochemistry. 1991; 30: 3328-3334Crossref PubMed Scopus (91) Google Scholar;Gahmberg et al., 1992Gahmberg C.G. Kotovuori P. Tontti E. Cell surface carbohydrate in cell adhesion. Sperm cells and leukocytes bind to their target cells through specific oligosaccharide ligands.Apmis. 1992; 100 (Suppl. 27): 39-52Crossref PubMed Scopus (12) Google Scholar;Miyake et al., 1992Miyake M. Taki T. Hitomi S. Hakomori S. Correlation of expression of H/Ley/Leb antigens with survival in patients with carcinoma of the lung.N Engl J Med. 1992; 327: 14-18Crossref PubMed Scopus (225) Google Scholar;Dabelsteen, 1996Dabelsteen E. Cell surface carbohydrates as prognostic markers in human carcinomas.J Pathol. 1996; 179: 358-369Crossref PubMed Scopus (226) Google Scholar;Ichikawa et al., 1997Ichikawa D. Handa K. Withers D.A. Hakomori S. Histo-blood group A/B versus H status of human carcinoma cells as correlated with haptotactic cell motility: approach with A and B gene transfection.Cancer Res. 1997; 57: 3092-3096PubMed Google Scholar). In neoplastic tissues marked alterations in the normal patterns of expression of cell surface carbohydrates are found and seem to be related to tumor behavior (Muramatsu, 1993Muramatsu T. Carbohydrate signals in metastasis and prognosis of human carcinomas.Glycobiology. 1993; 3: 291-296Crossref PubMed Scopus (138) Google Scholar;Dabelsteen, 1996Dabelsteen E. Cell surface carbohydrates as prognostic markers in human carcinomas.J Pathol. 1996; 179: 358-369Crossref PubMed Scopus (226) Google Scholar;Ichikawa et al., 1997Ichikawa D. Handa K. Withers D.A. Hakomori S. Histo-blood group A/B versus H status of human carcinoma cells as correlated with haptotactic cell motility: approach with A and B gene transfection.Cancer Res. 1997; 57: 3092-3096PubMed Google Scholar). The active movement of epithelial cells that occurs during wound healing is another process that is associated with changes in the patterns of expression of cell surface carbohydrates and other adhesion-related macromolecules (Dabelsteen and Fejerskov, 1974Dabelsteen E. Fejerskov O. Loss of epithelial blood group antigen-A during wound healing in oral mucous membrane.Acta Pathol Microbiol Scand Sect a. 1974; 84: 431-434Google Scholar;Mackenzie et al., 1977Mackenzie I.C. Dabelsteen E. Zimmermann K. The relationship between expression of epithelial B-like blood group antigen, cell movement and cell proliferation.Acta Pathol Microbiol Scand Sect a. 1977; 85: 49-56Google Scholar;Elenius et al., 1991Elenius K. Vainio S. Laato M. Salmivirta M. Theslev I. Jalkanen M. Induced expression of syndecan in healing wounds.J Cell Biol. 1991; 114: 585-595Crossref PubMed Scopus (187) Google Scholar;Larjava et al., 1993Larjava H. Salo T. Haapasalmi K. Kramer R.H. Heino J. Expression of integrins and basement components by wounded keratinocytes.J Clin Invest. 1993; 92: 1425-1435Crossref PubMed Scopus (324) Google Scholar). Comparison of the altered glycosylation patterns of epithelial cells in healing wounds and in malignancy might therefore provide additional information about which changes are likely to be functionally related to increased cell motility. Previous work indicates that cell surface carbohydrates represented by the ABO blood group antigens, and particularly the related structure Ley, are likely to be of functional interest to cell movement and it has been shown that tumor cell migration in vitro can be inhibited by antibodies to Ley (Vowden et al., 1986Vowden P. Lowe A.D. Lennox E.S. Bleehen N.M. The expression of ABH and Y blood group antigens in benign and malignant breast tissue: The preservation of the H and Y antigens in malignant epithelium.Br J Cancer. 1986; 53: 313-319Crossref PubMed Scopus (26) Google Scholar;Dejana et al., 1991Dejana E. Martin-padura I. Lauri D. et al.Endothelial leukocyte adhesion molecule-1-dependent adhesion of colon carcinoma cells to vascular endothelium is inhibited by an antibody to Lewis fucosylated type 1 carbohydrate chain.Lab Invest. 1991; 66: 324-330Google Scholar;Miyake and Hakomori, 1991Miyake M. Hakomori S. A specific cell surface glycoconjugate controlling cell motility: evidence by functional monoclonal antibodies that inhibit cell motility and tumor cell metastasis.Biochemistry. 1991; 30: 3328-3334Crossref PubMed Scopus (91) Google Scholar;Singhal, 1991Singhal A.K. Histo-blood group antigens in cancer.Cancer Biol. 1991; 2: 379-388Google Scholar;Muramatsu, 1993Muramatsu T. Carbohydrate signals in metastasis and prognosis of human carcinomas.Glycobiology. 1993; 3: 291-296Crossref PubMed Scopus (138) Google Scholar). The primary aim of this study was to examine the migrating epithelial cells of experimental oral wounds for the expression of Ley and its biosynthetically related carbohydrates; however, as very little information could be found about the effects of wounding on the expression of other oral epithelial differentiation markers, we also examined the expression of cytokeratins and basal lamina components at the wound margin in order to define the context in which changes in cell surface carbohydrates occur. Standardized oral wounds were made, with informed consent, in nine healthy young adult volunteers. The primary wounds were shallow but included the full epithelial thickness. They were made with a 3 mm biopsy punch either in the buccal mucosa distal to the angle of the mouth or in the mucosa of the buccal sulcus in the upper canine region, and the samples for study were collected using a 4 mm biopsy punch to remove the wounded area together with the surrounding wound margins (Dabelsteen and Fejerskov, 1974Dabelsteen E. Fejerskov O. Loss of epithelial blood group antigen-A during wound healing in oral mucous membrane.Acta Pathol Microbiol Scand Sect a. 1974; 84: 431-434Google Scholar). Six specimens were collected at 48 h, and three specimens at 72 h, after wounding. All specimens were frozen for cryotomy, sectioned at 5 μm, and air dried. The patients’ secretor status, which is the ability to secrete blood group antigens in saliva, was determined as previously described (Dabelsteen, 1972Dabelsteen E. Quantitative determination of blood group substances A of oral epithelial cells by immunofluorescence and immunoperoxidase methods.Acta Pathol Microbiol Scand Sect a. 1972; 80: 847-853PubMed Google Scholar), as secretor status is known to result in a slightly different pattern of histologic distribution of the carbohydrates that were investigated (Mandel et al., 1988Mandel U. Clausen H. Vedtofte P. Scrensen H. Dabelsteen E. Sequential expression of carbohydrate antigens with precursor-product relation characterizes cellular maturation in stratified squamous epithelium.J Oral Pathol. 1988; 17: 506-511Crossref PubMed Scopus (26) Google Scholar). Of the six biopsies collected after 48 h, two were nonsecretors and four were secretors, and of the three specimens collected after 72 h, two were secretors and one was a nonsecretor. Several sections of each specimen were stained with hematoxylin and eosin to examine the general histologic appearance of the healing wounds. Immunohistochemical staining to display cell surface carbohydrates was performed with the panel of monoclonal antibodies (MoAb) shown in Table 1. This panel included antibodies with specificities for N-acetyl-lactosamine, Ley, H (type 2 chain), Lex, sialosyl-Lex, and sialosyl-Tn. These antigens are all precursor structures in the ABO blood group system (Clausen and Hakomori, 1989Clausen H. Hakomori S. ABH and related histo-blood group antigens; immunochemical differences in carrier isotypes and their distribution.Vox Sang. 1989; 56: 1-20Crossref PubMed Scopus (455) Google Scholar).Table 1Structure of carbohydrate antigens expessed on epithelial cells, the antibodies used to detect them, and the patterns of staining of oral epithelial wounds Open table in a new tab Cytoskeletal changes in the epithelial outgrowths were evaluated by staining sections with antibodies against a range of cytokeratins that are variously expressed in oral mucosae (Morgan et al., 1991Morgan P.R. Shirlaw P.J. Lane E.B. Leigh I.M. Johnson N.W. Cytoplasmic markers of disturbed epithelial differentiation as markers of high risk lesions with special reference to cytokeratins.in: Johnson N.W. Risk Markers for Oral Diseases. Oral Cancer. Cambridge University Press, Cambridge1991: 188-202Google Scholar;Mackenzie and Gao, 1993Mackenzie I.C. Gao Z. Patterns of cytokeratin expression in the epithelia of inflamed human gingiva and periodontal pockets.J Periodont Res. 1993; 28: 49-59Crossref PubMed Scopus (47) Google Scholar). These included MoAb against K5 and K14, cytokeratins that are typically expressed by the basal cells of stratifying epithelia; MoAb against K4 and K13, cytokeratins typically expressed in the suprabasal cells of buccal epithelium; MoAb against K16, a cytokeratin that is expressed in epidermis only when it is hyperplastic but is variously expressed in normal mucosal epithelia; MoAb against cytokeratin K19, which is reported to be present in basal epithelial cells of some nonkeratinizing oral mucosae and to be expressed in other epithelia as a result of inflammation (Ouhayoun et al., 1985Ouhayoun J.P. Gosselin S. Forest N. Winter S. Franke W.W. Cytokeratin patterns of human oral epithelia: differences in cytokeratin synthesis in gingival epithelium and the adjacent alveolar mucosa.Differentiation. 1985; 30: 123-129Crossref PubMed Scopus (103) Google Scholar,Ouhayoun et al., 1990Ouhayoun J.P. Goffaux J.C. Sawaf M.H. Shabana A.H. Collin C. Forest N. Changes in cytokeratin expression in gingiva during inflammation.J Periodontal Res. 1990; 25: 283-292Crossref PubMed Scopus (39) Google Scholar;Bosch et al., 1989Bosch F.X. Ouhayoun J.P. Bader B.L. Extensive changes in cytokeratin expression patterns in pathology affected human gingiva.Virchows Arch (B). 1989; 58: 59-77Crossref Scopus (90) Google Scholar); and MoAb against K8 and K18, cytokeratins that are typically expressed only in simple epithelia but are found in the stratifying junctional epithelium adjacent to the tooth (Moll et al., 1982Moll R. Franke W.W. Schiller D.L. Geiger B. Krepler R. The catalog of human cytokeratins, patterns of expression in normal epithelium, tumors and cultured cells.Cell. 1982; 31: 11-24Abstract Full Text PDF PubMed Scopus (4371) Google Scholar,Moll et al., 1989Moll R. Dhouailly D. Sun T.T. Expression of keratin 5 as a distinctive feature of epithelial and biphasic mesotheliomas. An immunohistochemical study using monoclonal antibody AE14.Virchows Arch (B). 1989; 58: 129-145Crossref Scopus (97) Google Scholar). To assess reformation of basal lamina, sections were stained with antibodies against laminin α5-chain and γ2-chain (laminin-5) with pemphigoid serum, and with an antibody against the 180 kd bullous pemphigoid antigen (Hopkinson et al., 1992Hopkinson S.B. Riddelle K.S. Jones J.C.R. Cytoplasmic domain of the 180-kD bullous pemphigoid antigen, a hemidesmosomal component: molecular and cell biologic characterization.J Invest Dermatol. 1992; 99: 264-270Crossref PubMed Scopus (123) Google Scholar). The antibodies with references to their specificity are shown in Table 2.Table 2Antibodies used to detect cytokeratins and basal lamina componentsAntigenAntibody and isotypeReferenceK5AE14 (IgG)Lynch et al., 1986Lynch M.H. Oguin W.M. Hardy C. Mak L. Sun T.-T. Acidic and basic hair/nail hard keratins: Their co-localization in upper cortical and cuticle cells of the human hair follicle and their relationship to soft keratins.J Cell Biol. 1986; 103: 2593-2606Crossref PubMed Scopus (289) Google ScholarK14LL001 (IgG2a)Purkis et al., 1990Purkis P.E. Steel J.B. Mackenzie I.C. Nathrath W.B. Leigh I.M. Lane E.B. Antibody markers of basal cells in complex epithelia.J Cell Sci. 1990; 97: 39-50Crossref PubMed Google ScholarK4IC7 (IgG2a)van Muijen et al., 1986van Muijen G.N.P. Ruiter D.J. Franke W.W. Achtstatter T. Hassnoot W.H.B. Ponec M. Warnaar S.O. Cell type heterogeneity of cytokeratin expression in complex epithelia and carcinomas as demonstrated by monoclonal antibodies specific for cytokeratins no. 4 and 13.Exp Cell Res. 1986; 162: 97-113Crossref PubMed Scopus (251) Google ScholarK13AE8 (IgG1)Dhouailly et al., 1989Dhouailly D. Xu C. Manabe M. Schermer A. Sun T.-T. Expression of hair-related keratins in a soft epithelium: subpopulations of human and mouse dorsal tongue keratinocytes express keratin markers for hair-, skin-, and esophageal-types of differentiation.Exp Cell Res. 1989; 181: 141-158Crossref PubMed Scopus (107) Google ScholarK16LL025 (IgG1)Purkis et al., 1990Purkis P.E. Steel J.B. Mackenzie I.C. Nathrath W.B. Leigh I.M. Lane E.B. Antibody markers of basal cells in complex epithelia.J Cell Sci. 1990; 97: 39-50Crossref PubMed Google ScholarK8LE41 (IgG1)Lane et al., 1982Lane E.D. Goodman S.L. Trejdosiewicz L.K. Disruption of the keratin filament network during epithelial cell division.EMBO. 1982; 1: 1365-1372PubMed Google ScholarK18LE61 (IgG1)Lane et al., 1982Lane E.D. Goodman S.L. Trejdosiewicz L.K. Disruption of the keratin filament network during epithelial cell division.EMBO. 1982; 1: 1365-1372PubMed Google ScholarK192P2K (IgG2a)Stasiak et al., 1989Stasiak P.C. Purkis P.E. Leigh I.M. Lane E.B. Keratin 19: predicted amino acid sequence and broad tissue distribution suggest it evolved from keratinocyte keratins.J Invest Dermatol. 1989; 92: 707-716Abstract Full Text PDF PubMed Google ScholarRCK108 (IgG1)Smedts et al., 1992Smedts F. Ramaekers F. Troyanovsky S. et al.Keratin expression in cervical cancer.Am J Pathol. 1992; 141: 497-511PubMed Google ScholarLaminin α5-chain4C7 (IgG2a)Engval et al., 1990Engval E. Earwicher D. Haaparanta T. Ruoslahti E. Sanes J.R. Distribution and isolation of four laminin variants; tissue restricted distribution of heterodimers assembled from five different subunits.Cell Regulation. 1990; 1: 731-740Google ScholarTiger et al., 1997Tiger C.F. Champliaud M.F. Pedrosa-domellof F. Thornell L.E. Ekblom P. Gullberg D. Presence of laminin alpha5 chain and lack of laminin alpha1 chain during human muscle development and in muscular dystrophies.J Biol Chem. 1997; 272: 28590-28595Crossref PubMed Scopus (189) Google ScholarLaminin γ2-chainB4–6 (IgG1)Gil et al., 1994Gil S.G. Brown T.A. Maureen C.R. William G.C. Junctional epidermolysis bullosis: defects in expression of epiligrin/nicein/kalinin and integrin β4 that inhibit hemidesmosome formation.J Invest Dermatol. 1994; 103: 31S-38SAbstract Full Text PDF PubMed Google ScholarCollagen IVCiV22 (IgG1)Odermatt et al., 1984Odermatt B.F. Lang A.B. Ruttner J.R. Wintherhalten K.H. Treb B. Monoclonal antibodies to human type IV collagen: Useful reagents to demonstrate the heterotrimeric nature of the molecule.Proc Natl Acad Sci. 1984; 81: 7343-7347Crossref PubMed Scopus (80) Google ScholarCollagen VIILH7.2 (IgG1)Leigh et al., 1987Leigh I.M. Purkis P.E. Navsaria H.A. Philips T.J. Treatment of chronic venous ulcers with sheets of cultured allogenic keratinocytes.Br J Dermatol. 1987; 117: 591-597Crossref PubMed Scopus (197) Google ScholarBP180rabbit polyclonalHopkinson et al., 1992Hopkinson S.B. Riddelle K.S. Jones J.C.R. Cytoplasmic domain of the 180-kD bullous pemphigoid antigen, a hemidesmosomal component: molecular and cell biologic characterization.J Invest Dermatol. 1992; 99: 264-270Crossref PubMed Scopus (123) Google Scholar Open table in a new tab Tissue antigens were detected using double-layer immunohistochemical staining techniques, as described previously in detail (Mandel et al., 1991Mandel U. Ørntoft T. Holmes E. Scrensen H. Clausen H. Hakomori S. Dabelsteen E. Lewis blood group antigens in salivary glands and stratified epithelium: Lack of regulation of Lewis antigen expression in ductal and buccal mucosal lining epithelia.Vox Sang. 1991; 61: 205-214Crossref PubMed Scopus (31) Google Scholar). Primary antibodies were applied overnight at 4°C and fluoroscein isothiocyanate- or alkaline phosphatase-conjugated rabbit antibodies against mouse, rat, or human immunoglobulins (DAKO, Copenhagen, Denmark), as appropriate, were used as the second layer. In order to confirm apparent differences in the degree of expression of some of the molecules of interest, a double dilution serial titration was performed with some of the primary antibodies (Dabelsteen, 1972Dabelsteen E. Quantitative determination of blood group substances A of oral epithelial cells by immunofluorescence and immunoperoxidase methods.Acta Pathol Microbiol Scand Sect a. 1972; 80: 847-853PubMed Google Scholar). Sections incubated with fluoroscein isothiocyanate-conjugated second layer antibodies were mounted in buffered glycerol containing paraphenylenediamine as an anti-fading agent (Johnson and Araujo, 1981Johnson G.D. Araujo N.G.M. A simple method of reducing the fading of immunofluorescence during microscopy.J Immunol Meth. 1981; 43: 349-350Crossref PubMed Scopus (1610) Google Scholar), and examined using a Leitz fluorescence microscope equipped with fluoroscein isothiocyanate interference filters and a 100 W HBO lamp. Sections incubated with second layer antibodies conjugated to alkaline phosphatase were histochemically processed (Bryne et al., 1991Bryne M. Reibel J. Mandel U. Dabelsteen E. Expression of mucin type carbohydrates may (Suppl.)histologic diagnosis in oral premalignant lesions.J Oral Pathol Med. 1991; 20: 120-125Crossref PubMed Scopus (24) Google Scholar) and mounted in “Aquamount” (Gurr, BDH, U.K.). Various control reactions for specificity of staining included omission of primary antibody, staining with mouse monoclonal antibodies of similar isotypes but of irrelevant specificities to primary antibodies, and substitution of hybridoma supernatant with supernatant from the Sp2 myeloma cell line used for hybridization. The basic histologic pattern of healing was similar for all wounds. Hematoxylin and eosin stained sections showed that epithelial outgrowths from each of the wound margins passed down into and across a wound bed that was filled with fibrin and inflammatory cells. In all specimens the region of junction between the original epithelium at the wound margin and the newly formed outgrowth of epithelium could be clearly identified by the position of severed collagen bundles in the underlying connective tissue. There was some individual variation in the degree of epithelial outgrowth but the 48 h specimens typically showed only small outgrowths of epithelial cells (Figure 2c later), whereas the 72 h specimens formed more extensive outgrowths that covered a large part of the wound bed Figure 1. The antibodies against laminin α5-chain and laminin γ2-chain (laminin-5), against collagens IV and VII, and against the 180 kDa bullous pemphigoid antigen, all showed a similar pattern of linear staining of the basal lamina region beneath the unwounded epithelium Figure 1. The basement membrane region beneath the migrating epithelium did not stain with the antibodies against laminin α5-chain or against collagen IV. Staining of collagen VII was seen under the epithelial outgrowth except at the leading edge. Titration of primary antibody showed that the staining beneath the outgrowth was weaker than beneath the unwounded epithelium, but a characteristic pattern of positive staining was always seen in the cytoplasm of all of the basal cells of the outgrowth. Compared with the normal epithelium, the outgrowth region, and also the basement membrane region proximal to the wound margin, appeared to stain more strongly for laminin γ2-chain (laminin-5) Figure 1. The antibodies isolated from bullous pemphigoid patients stained the basement membrane region beneath the unwounded epithelium, but no staining in the epithelial outgrowth region was seen with these sera (results not shown); however, the antibodies specific for the 180 kDa bullous pemphigoid antigen stained beneath the entire length of the epithelial outgrowth Figure 2b. The normal epithelium distant from the wound margins showed a pattern of cytokeratin staining essentially similar to that previously described for normal buccal mucosa (Bosch et al., 1989Bosch F.X. Ouhayoun J.P. Bader B.L. Extensive changes in cytokeratin expression patterns in pathology affected human gingiva.Virchows Arch (B). 1989; 58: 59-77Crossref Scopus (90) Google Scholar;Morgan et al., 1991Morgan P.R. Shirlaw P.J. Lane E.B. Leigh I.M. Johnson N.W. Cytoplasmic markers of disturbed epithelial differentiation as markers of high risk lesions with special reference to cytokeratins.in: Johnson N.W. Risk Markers for Oral Diseases. Oral Cancer. Cambridge University Press, Cambridge1991: 188-202Google Scholar). Staining for K5 was mainly restricted to basal cells but extended through the full epithelial thickness for K14. Although K5 and K14 are both predominantly synthesized in basal cells according to in situ hybridization data (Stoler et al., 1988Stoler A. Kopan R. Duvic M. Fuchs E. Use of monospecific antisera and cRNA probes to localize the major changes in keratin expression during normal and abnormal epidermal differentiation.J Cell Biol. 1988; 107: 427-446Crossref PubMed Scopus (285) Google Scholar), the K5 protein is reported normally to lose reactivity in the suprabasal layers (Purkis et al., 1990Purkis P.E. Steel J.B. Mackenzie I.C. Nathrath W.B. Leigh I.M. Lane E.B. Antibody markers of basal cells in complex epithelia.J Cell Sci. 1990; 97: 39-50Crossref PubMed Google Scholar). The unwounded epithelium showed strong and uniform suprabasal staining for K4 and K13 and a patchy distribution of suprabasal cells staining for K16. Staining for K19 was found in only one biopsy specimen that showed staining of basal and some parabasal cells of the unwounded epithelium Figure 1. The epithelial outgrowths from the wound margins showed a consistent pattern of changes in keratin expression. As in the normal epithelium, the epithelium of the outgrowth region showed uniform staining of the full epithelial thickness for K14, but basal cell staining for K5 Figure 2d was slightly reduced and in some wounds was patchy. Little staining for K4 and K13 was seen in epithelial outgrowths of the 2 d specimens, but, except for the leading edge of migrating cells, the 3 d specimens showed staining of the suprabasal strata of outgrowth epithelium for K4 and K13 Figure 2a. Unlike the normal epithelium, K16 was uniformly present in all cell layers of all regions of the epithelial outgrowths and expression of K16 also extended back into the unwounded epithelium proximal to the wound margin Figure 1. Only the specimen that showed K19 expression in the normal epithelium showed any staining for K19 in the outgrowth region; here a pattern of basal and scattered suprabasal cell staining was seen similar to that of the unwounded epithelium Figure 2. No staining for K8 or K18 was found in either the normal or the outgrowth epithelium of any of the specimens (staining not shown). In the normal epithelium distant from the wound there was moderate (secretors) to weak (nonsecretors) staining with the antibody against Ley, but the epithelial outgrowths of all specimens were strongly stained Table 1. Titration of the primary antibody confirmed stronger Ley expression with all specimens with a greater than three step difference found between endpoint titers for the outgrowth and unwounded epithelial regions. Strong expression of Ley on the epithelial outgrowth did not appear to be influenced by secretor status Figure 1, 3. A further difference between normal and outgrowth epithelium was that the weak staining for Ley that was present in normal epithelium was restricted to spinou" @default.
• W2094693609 created "2016-06-24" @default.
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• W2094693609 date "1998-10-01" @default.
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• W2094693609 title "Altered Expression of Epithelial Cell Surface Glycoconjugates and Intermediate Filaments at the Margins of Mucosal Wounds" @default.
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