Abstract
L-selectin (leukocyte adhesion molecule 1/MEL-14), a member of the selectin family of cell adhesion molecules, mediates leukocyte rolling and leukocyte adhesion to endothelium at sites of inflammation. In addition, L-selectin mediates the binding of lymphocytes to high endothelial venules (HEV) of peripheral lymph nodes. The strong amino acid sequence conservation of the cytoplasmic domain of L-selectin between humans and mice suggests an important role for this region. Deletion of the COOH-terminal 11 amino acids from the approximately 17 amino acid cytoplasmic domain of L-selectin eliminated binding of lymphocytes to HEV in the in vitro frozen section assay, and also abolished leukocyte rolling in vivo in exteriorized rat mesenteric venules, but did not alter the lectin activity of L-selectin. Pretreatment of cells with cytochalasin B, which disrupts actin microfilaments, also abolished adhesion without affecting carbohydrate recognition. Therefore, the cytoplasmic domain of L-selectin regulates leukocyte adhesion to endothelium independent of ligand recognition, by controlling cytoskeletal interactions and/or receptor avidity.
Full Text
The Full Text of this article is available as a PDF (2.1 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Alt F., Rosenberg N., Lewis S., Thomas E., Baltimore D. Organization and reorganization of immunoglobulin genes in A-MULV-transformed cells: rearrangement of heavy but not light chain genes. Cell. 1981 Dec;27(2 Pt 1):381–390. doi: 10.1016/0092-8674(81)90421-9. [DOI] [PubMed] [Google Scholar]
- Atherton A., Born G. V. Quantitative investigations of the adhesiveness of circulating polymorphonuclear leucocytes to blood vessel walls. J Physiol. 1972 Apr;222(2):447–474. doi: 10.1113/jphysiol.1972.sp009808. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bevilacqua M. P., Stengelin S., Gimbrone M. A., Jr, Seed B. Endothelial leukocyte adhesion molecule 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins. Science. 1989 Mar 3;243(4895):1160–1165. doi: 10.1126/science.2466335. [DOI] [PubMed] [Google Scholar]
- Bowen B. R., Nguyen T., Lasky L. A. Characterization of a human homologue of the murine peripheral lymph node homing receptor. J Cell Biol. 1989 Jul;109(1):421–427. doi: 10.1083/jcb.109.1.421. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cepko C. L., Roberts B. E., Mulligan R. C. Construction and applications of a highly transmissible murine retrovirus shuttle vector. Cell. 1984 Jul;37(3):1053–1062. doi: 10.1016/0092-8674(84)90440-9. [DOI] [PubMed] [Google Scholar]
- Disdier M., Morrissey J. H., Fugate R. D., Bainton D. F., McEver R. P. Cytoplasmic domain of P-selectin (CD62) contains the signal for sorting into the regulated secretory pathway. Mol Biol Cell. 1992 Mar;3(3):309–321. doi: 10.1091/mbc.3.3.309. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fiebig E., Ley K., Arfors K. E. Rapid leukocyte accumulation by "spontaneous" rolling and adhesion in the exteriorized rabbit mesentery. Int J Microcirc Clin Exp. 1991 May;10(2):127–144. [PubMed] [Google Scholar]
- Glabe C. G., Harty P. K., Rosen S. D. Preparation and properties of fluorescent polysaccharides. Anal Biochem. 1983 Apr 15;130(2):287–294. doi: 10.1016/0003-2697(83)90590-0. [DOI] [PubMed] [Google Scholar]
- Hayashi Y., Haimovich B., Reszka A., Boettiger D., Horwitz A. Expression and function of chicken integrin beta 1 subunit and its cytoplasmic domain mutants in mouse NIH 3T3 cells. J Cell Biol. 1990 Jan;110(1):175–184. doi: 10.1083/jcb.110.1.175. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hibbs M. L., Jakes S., Stacker S. A., Wallace R. W., Springer T. A. The cytoplasmic domain of the integrin lymphocyte function-associated antigen 1 beta subunit: sites required for binding to intercellular adhesion molecule 1 and the phorbol ester-stimulated phosphorylation site. J Exp Med. 1991 Nov 1;174(5):1227–1238. doi: 10.1084/jem.174.5.1227. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hibbs M. L., Xu H., Stacker S. A., Springer T. A. Regulation of adhesion of ICAM-1 by the cytoplasmic domain of LFA-1 integrin beta subunit. Science. 1991 Mar 29;251(5001):1611–1613. doi: 10.1126/science.1672776. [DOI] [PubMed] [Google Scholar]
- Imai Y., True D. D., Singer M. S., Rosen S. D. Direct demonstration of the lectin activity of gp90MEL, a lymphocyte homing receptor. J Cell Biol. 1990 Sep;111(3):1225–1232. doi: 10.1083/jcb.111.3.1225. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Johnston G. I., Cook R. G., McEver R. P. Cloning of GMP-140, a granule membrane protein of platelets and endothelium: sequence similarity to proteins involved in cell adhesion and inflammation. Cell. 1989 Mar 24;56(6):1033–1044. doi: 10.1016/0092-8674(89)90636-3. [DOI] [PubMed] [Google Scholar]
- Kansas G. S., Spertini O., Stoolman L. M., Tedder T. F. Molecular mapping of functional domains of the leukocyte receptor for endothelium, LAM-1. J Cell Biol. 1991 Jul;114(2):351–358. doi: 10.1083/jcb.114.2.351. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kansas G. S., Wood G. S., Dailey M. O. A family of cell-surface glycoproteins defined by a putative anti-endothelial cell receptor antibody in man. J Immunol. 1989 May 1;142(9):3050–3057. [PubMed] [Google Scholar]
- Lasky L. A. Selectins: interpreters of cell-specific carbohydrate information during inflammation. Science. 1992 Nov 6;258(5084):964–969. doi: 10.1126/science.1439808. [DOI] [PubMed] [Google Scholar]
- Lasky L. A., Singer M. S., Yednock T. A., Dowbenko D., Fennie C., Rodriguez H., Nguyen T., Stachel S., Rosen S. D. Cloning of a lymphocyte homing receptor reveals a lectin domain. Cell. 1989 Mar 24;56(6):1045–1055. doi: 10.1016/0092-8674(89)90637-5. [DOI] [PubMed] [Google Scholar]
- Lesley J., He Q., Miyake K., Hamann A., Hyman R., Kincade P. W. Requirements for hyaluronic acid binding by CD44: a role for the cytoplasmic domain and activation by antibody. J Exp Med. 1992 Jan 1;175(1):257–266. doi: 10.1084/jem.175.1.257. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lewinsohn D. M., Bargatze R. F., Butcher E. C. Leukocyte-endothelial cell recognition: evidence of a common molecular mechanism shared by neutrophils, lymphocytes, and other leukocytes. J Immunol. 1987 Jun 15;138(12):4313–4321. [PubMed] [Google Scholar]
- Ley K., Gaehtgens P. Endothelial, not hemodynamic, differences are responsible for preferential leukocyte rolling in rat mesenteric venules. Circ Res. 1991 Oct;69(4):1034–1041. doi: 10.1161/01.res.69.4.1034. [DOI] [PubMed] [Google Scholar]
- Ley K., Gaehtgens P., Fennie C., Singer M. S., Lasky L. A., Rosen S. D. Lectin-like cell adhesion molecule 1 mediates leukocyte rolling in mesenteric venules in vivo. Blood. 1991 Jun 15;77(12):2553–2555. [PubMed] [Google Scholar]
- Ley K., Pries A. R., Gaehtgens P. A versatile intravital microscope design. Int J Microcirc Clin Exp. 1987;6(2):161–167. [PubMed] [Google Scholar]
- Marcantonio E. E., Guan J. L., Trevithick J. E., Hynes R. O. Mapping of the functional determinants of the integrin beta 1 cytoplasmic domain by site-directed mutagenesis. Cell Regul. 1990 Jul;1(8):597–604. doi: 10.1091/mbc.1.8.597. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ohmori H., Toyama S., Toyama S. Direct proof that the primary site of action of cytochalasin on cell motility processes is actin. J Cell Biol. 1992 Feb;116(4):933–941. doi: 10.1083/jcb.116.4.933. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pardi R., Inverardi L., Rugarli C., Bender J. R. Antigen-receptor complex stimulation triggers protein kinase C-dependent CD11a/CD18-cytoskeleton association in T lymphocytes. J Cell Biol. 1992 Mar;116(5):1211–1220. doi: 10.1083/jcb.116.5.1211. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pries A. R. A versatile video image analysis system for microcirculatory research. Int J Microcirc Clin Exp. 1988 Nov;7(4):327–345. [PubMed] [Google Scholar]
- Siegelman M. H., Weissman I. L. Human homologue of mouse lymph node homing receptor: evolutionary conservation at tandem cell interaction domains. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5562–5566. doi: 10.1073/pnas.86.14.5562. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Siegelman M. H., van de Rijn M., Weissman I. L. Mouse lymph node homing receptor cDNA clone encodes a glycoprotein revealing tandem interaction domains. Science. 1989 Mar 3;243(4895):1165–1172. doi: 10.1126/science.2646713. [DOI] [PubMed] [Google Scholar]
- Solowska J., Edelman J. M., Albelda S. M., Buck C. A. Cytoplasmic and transmembrane domains of integrin beta 1 and beta 3 subunits are functionally interchangeable. J Cell Biol. 1991 Sep;114(5):1079–1088. doi: 10.1083/jcb.114.5.1079. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Spertini O., Kansas G. S., Munro J. M., Griffin J. D., Tedder T. F. Regulation of leukocyte migration by activation of the leukocyte adhesion molecule-1 (LAM-1) selectin. Nature. 1991 Feb 21;349(6311):691–694. doi: 10.1038/349691a0. [DOI] [PubMed] [Google Scholar]
- Spertini O., Kansas G. S., Reimann K. A., Mackay C. R., Tedder T. F. Function and evolutionary conservation of distinct epitopes on the leukocyte adhesion molecule-1 (TQ-1, Leu-8) that regulate leukocyte migration. J Immunol. 1991 Aug 1;147(3):942–949. [PubMed] [Google Scholar]
- Springer T. A. Adhesion receptors of the immune system. Nature. 1990 Aug 2;346(6283):425–434. doi: 10.1038/346425a0. [DOI] [PubMed] [Google Scholar]
- Stamper H. B., Jr, Woodruff J. J. Lymphocyte homing into lymph nodes: in vitro demonstration of the selective affinity of recirculating lymphocytes for high-endothelial venules. J Exp Med. 1976 Sep 1;144(3):828–833. doi: 10.1084/jem.144.3.828. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stoolman L. M. Adhesion molecules controlling lymphocyte migration. Cell. 1989 Mar 24;56(6):907–910. doi: 10.1016/0092-8674(89)90620-x. [DOI] [PubMed] [Google Scholar]
- Tedder T. F., Isaacs C. M., Ernst T. J., Demetri G. D., Adler D. A., Disteche C. M. Isolation and chromosomal localization of cDNAs encoding a novel human lymphocyte cell surface molecule, LAM-1. Homology with the mouse lymphocyte homing receptor and other human adhesion proteins. J Exp Med. 1989 Jul 1;170(1):123–133. doi: 10.1084/jem.170.1.123. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thomas L., Byers H. R., Vink J., Stamenkovic I. CD44H regulates tumor cell migration on hyaluronate-coated substrate. J Cell Biol. 1992 Aug;118(4):971–977. doi: 10.1083/jcb.118.4.971. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Woodruff J. J., Katz M., Lucas L. E., Stamper H. B., Jr An in vitro model of lymphocyte homing. II. Membrane and cytoplasmic events involved in lymphocyte adherence to specialized high-endothelial venules of lymph nodes. J Immunol. 1977 Nov;119(5):1603–1610. [PubMed] [Google Scholar]
- von Andrian U. H., Chambers J. D., McEvoy L. M., Bargatze R. F., Arfors K. E., Butcher E. C. Two-step model of leukocyte-endothelial cell interaction in inflammation: distinct roles for LECAM-1 and the leukocyte beta 2 integrins in vivo. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7538–7542. doi: 10.1073/pnas.88.17.7538. [DOI] [PMC free article] [PubMed] [Google Scholar]