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Tenascin supports lymphocyte rolling.

Clark RA, Erickson HP, Springer TA - J. Cell Biol. (1997)

Bottom Line: Tenascin has been reported to have both adhesive and anti-adhesive effects in static assays.When compared to rolling of the same cell type on E-selectin, rolling on tenascin was found to be smoother at all shear stresses tested, suggesting that cells formed a larger number of bonds on the tenascin substrate than on the E-selectin substrate.When protein plating densities were adjusted to give similar profiles of cell detachment under increasing shears, the density of tenascin was 8.5-fold greater than that of E-selectin.

View Article: PubMed Central - PubMed

Affiliation: The Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.

ABSTRACT
Tenascin is a large extracellular matrix molecule expressed at specific sites in the adult, including immune system tissues such as the bone marrow, thymus, spleen, and T cell areas of lymph nodes. Tenascin has been reported to have both adhesive and anti-adhesive effects in static assays. We report here that tenascin supports the tethering and rolling of lymphocytes and lymphoblastic cell lines under flow conditions. Binding was calcium dependent and was not inhibited by treatment of lymphocytes with O-glycoprotease or a panel of glycosidases including neuraminidase and heparitinase but was inhibited by treatment of cells with proteinase K. Binding was to the fibrinogen-like terminal domain of tenascin as determined by antibody blocking studies and binding to recombinant tenascin proteins. When compared to rolling of the same cell type on E-selectin, rolling on tenascin was found to be smoother at all shear stresses tested, suggesting that cells formed a larger number of bonds on the tenascin substrate than on the E-selectin substrate. When protein plating densities were adjusted to give similar profiles of cell detachment under increasing shears, the density of tenascin was 8.5-fold greater than that of E-selectin. Binding to tenascin was not dependent on any molecules previously identified as tenascin receptors and is likely to involve a novel tenascin receptor on lymphocytes. We postulate that the ability of tenascin to support lymphocyte rolling may reflect its ability to support cell migration and that this interaction may be used by lymphocytes migrating through secondary lymphoid organs.

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Immunofluorescent staining of human tonsil with tenascin mAb M168. Tenascin is heavily expressed by HEV and the  reticular fiber network of the interfollicular T cell areas, while B  cell follicles show sparse expression. “F” denotes a B cell follicle;  three prominent HEV are visible below the follicle.
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Figure 9: Immunofluorescent staining of human tonsil with tenascin mAb M168. Tenascin is heavily expressed by HEV and the reticular fiber network of the interfollicular T cell areas, while B cell follicles show sparse expression. “F” denotes a B cell follicle; three prominent HEV are visible below the follicle.

Mentions: Tenascin is expressed in several hematopoetic and lymphoid tissues including bone marrow (37), thymus (32), spleen (43), lymph node, tonsil, and Peyer's patches (11, and Clark, R.A., unpublished observations). In the lymph node and tonsil, tenascin is expressed in the reticular fibers of the T cell areas as well as the basal surfaces of HEVs, suggesting a role in cell migration as opposed to lymphocyte binding to the luminal surface of HEVs (Fig. 9). Previous studies have suggested that during lymphocyte migration through secondary lymphoid organs, lymphocytes may migrate along the reticular fiber network via adhesive interactions with the ECM components of these fibers (14, 15, 38). Although the rolling adhesions that we have demonstrated in vitro are not likely to occur in vivo in secondary lymphoid organs, the dynamic nature of this interaction may be well suited to support cellular migration. The dynamic reversibility of bonds formed between a cell and the substrate is a key part of cellular migration (23). Lymphocytes form bonds with tenascin that are sufficiently strong to tether the cell to the substrate but not strong enough to induce cell arrest and sticking. Migration speed has been suggested to be biphasic with respect to attachment strengths; low attachment strengths do not permit the transmission of the motile force within the cell to the substrate, intermediate attachment strengths produce the fastest migration, and higher attachment strengths produce cell arrest and spreading (19, 40). Indeed, the speed of smooth muscle cell migration on fibronectin and type IV collagen substrates was found to be fastest at intermediate attachment strengths (19). Thus, we predict that the ability of tenascin to support lymphocyte rolling may also reflect the ability of this protein to support cellular migration. Alternatively, cells may simultaneously bind to tenascin through a labile interaction that does not impede but may help guide the direction of cell migration, and to other extracellular matrix components through firmer adhesive interactions that may provide traction for migration but not directionality cues.


Tenascin supports lymphocyte rolling.

Clark RA, Erickson HP, Springer TA - J. Cell Biol. (1997)

Immunofluorescent staining of human tonsil with tenascin mAb M168. Tenascin is heavily expressed by HEV and the  reticular fiber network of the interfollicular T cell areas, while B  cell follicles show sparse expression. “F” denotes a B cell follicle;  three prominent HEV are visible below the follicle.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2139881&req=5

Figure 9: Immunofluorescent staining of human tonsil with tenascin mAb M168. Tenascin is heavily expressed by HEV and the reticular fiber network of the interfollicular T cell areas, while B cell follicles show sparse expression. “F” denotes a B cell follicle; three prominent HEV are visible below the follicle.
Mentions: Tenascin is expressed in several hematopoetic and lymphoid tissues including bone marrow (37), thymus (32), spleen (43), lymph node, tonsil, and Peyer's patches (11, and Clark, R.A., unpublished observations). In the lymph node and tonsil, tenascin is expressed in the reticular fibers of the T cell areas as well as the basal surfaces of HEVs, suggesting a role in cell migration as opposed to lymphocyte binding to the luminal surface of HEVs (Fig. 9). Previous studies have suggested that during lymphocyte migration through secondary lymphoid organs, lymphocytes may migrate along the reticular fiber network via adhesive interactions with the ECM components of these fibers (14, 15, 38). Although the rolling adhesions that we have demonstrated in vitro are not likely to occur in vivo in secondary lymphoid organs, the dynamic nature of this interaction may be well suited to support cellular migration. The dynamic reversibility of bonds formed between a cell and the substrate is a key part of cellular migration (23). Lymphocytes form bonds with tenascin that are sufficiently strong to tether the cell to the substrate but not strong enough to induce cell arrest and sticking. Migration speed has been suggested to be biphasic with respect to attachment strengths; low attachment strengths do not permit the transmission of the motile force within the cell to the substrate, intermediate attachment strengths produce the fastest migration, and higher attachment strengths produce cell arrest and spreading (19, 40). Indeed, the speed of smooth muscle cell migration on fibronectin and type IV collagen substrates was found to be fastest at intermediate attachment strengths (19). Thus, we predict that the ability of tenascin to support lymphocyte rolling may also reflect the ability of this protein to support cellular migration. Alternatively, cells may simultaneously bind to tenascin through a labile interaction that does not impede but may help guide the direction of cell migration, and to other extracellular matrix components through firmer adhesive interactions that may provide traction for migration but not directionality cues.

Bottom Line: Tenascin has been reported to have both adhesive and anti-adhesive effects in static assays.When compared to rolling of the same cell type on E-selectin, rolling on tenascin was found to be smoother at all shear stresses tested, suggesting that cells formed a larger number of bonds on the tenascin substrate than on the E-selectin substrate.When protein plating densities were adjusted to give similar profiles of cell detachment under increasing shears, the density of tenascin was 8.5-fold greater than that of E-selectin.

View Article: PubMed Central - PubMed

Affiliation: The Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.

ABSTRACT
Tenascin is a large extracellular matrix molecule expressed at specific sites in the adult, including immune system tissues such as the bone marrow, thymus, spleen, and T cell areas of lymph nodes. Tenascin has been reported to have both adhesive and anti-adhesive effects in static assays. We report here that tenascin supports the tethering and rolling of lymphocytes and lymphoblastic cell lines under flow conditions. Binding was calcium dependent and was not inhibited by treatment of lymphocytes with O-glycoprotease or a panel of glycosidases including neuraminidase and heparitinase but was inhibited by treatment of cells with proteinase K. Binding was to the fibrinogen-like terminal domain of tenascin as determined by antibody blocking studies and binding to recombinant tenascin proteins. When compared to rolling of the same cell type on E-selectin, rolling on tenascin was found to be smoother at all shear stresses tested, suggesting that cells formed a larger number of bonds on the tenascin substrate than on the E-selectin substrate. When protein plating densities were adjusted to give similar profiles of cell detachment under increasing shears, the density of tenascin was 8.5-fold greater than that of E-selectin. Binding to tenascin was not dependent on any molecules previously identified as tenascin receptors and is likely to involve a novel tenascin receptor on lymphocytes. We postulate that the ability of tenascin to support lymphocyte rolling may reflect its ability to support cell migration and that this interaction may be used by lymphocytes migrating through secondary lymphoid organs.

Show MeSH
Related in: MedlinePlus