SHAP Potentiates the CD44-mediated Leukocyte Adhesion to the Hyaluronan Substratum*

CD44-hyaluronan (HA) interaction is involved in diverse physiological and pathological processes. Regulation of interacting avidity is well studied on CD44 but rarely on HA. We discovered a unique covalent modification of HA with a protein, SHAP, that corresponds to the heavy chains of inter-α-trypsin inhibitor family molecules circulating in blood. Formation of the SHAP·HA complex is often associated with inflammation, a well known process involving the CD44-HA interaction. We therefore examined the effect of SHAP on the CD44-HA interaction-mediated lymphocyte adhesion. Under both static and flowing conditions, Hut78 cells (CD44-positive) and CD44-transfected Jurkat cells (originally CD44-negative) adhered preferentially to the immobilized SHAP·HA complex than to HA. The enhanced adhesion is exclusively mediated by the CD44-HA interaction, because it was inhibited by HA, but not IαI, and was completely abolished by pretreating the cells with anti-CD44 antibodies. SHAP appears to potentiate the interaction by increasing the avidity of HA to CD44 and altering their distribution on cell surfaces. Large amounts of the SHAP·HA complex accumulate in the hyperplastic synovium of rheumatoid arthritis patients. Leukocytes infiltrated to the synovium were strongly positive for HA, SHAP, and CD44 on their surfaces, suggesting a role for the adhesion-enhancing effect of SHAP in pathogenesis.

[1]  Marilyn S. Rugg,et al.  Characterization of Complexes Formed between TSG-6 and Inter-α-inhibitor That Act as Intermediates in the Covalent Transfer of Heavy Chains onto Hyaluronan* , 2005, Journal of Biological Chemistry.

[2]  J. Enghild,et al.  The TSG-6 and IαI Interaction Promotes a Transesterification Cleaving the Protein-Glycosaminoglycan-Protein (PGP) Cross-link*[boxs] , 2005, Journal of Biological Chemistry.

[3]  E. Balazs,et al.  Extended, relaxed, and condensed conformations of hyaluronan observed by atomic force microscopy. , 2005, Biophysical journal.

[4]  Marilyn S. Rugg,et al.  TSG-6 Modulates the Interaction between Hyaluronan and Cell Surface CD44*[boxs] , 2004, Journal of Biological Chemistry.

[5]  T. Wight,et al.  Proteoglycans in atherosclerosis and restenosis: key roles for versican. , 2004, Circulation research.

[6]  J. Antin,et al.  CD44-hyaluronic acid interactions mediate shear-resistant binding of lymphocytes to dermal endothelium in acute cutaneous GVHD. , 2004, Blood.

[7]  K. Kimata,et al.  Chapter 9 – Biological Function of SHAP–Hyaluronan Covalent Complex , 2004 .

[8]  G. Turner,et al.  Membrane protein glycosylation and CD44 content in the adhesion of human ovarian cancer cells to hyaluronan , 2004, Clinical & Experimental Metastasis.

[9]  M. Mörgelin,et al.  Molecular Heterogeneity of the SHAP-Hyaluronan Complex , 2003, Journal of Biological Chemistry.

[10]  C. A. de la Motte,et al.  Copyright © American Society for Investigative Pathology Mononuclear Leukocytes Bind to Specific Hyaluronan Structures on Colon Mucosal Smooth Muscle Cells Treated with Polyinosinic Acid:Polycytidylic Acid Inter-�-Trypsin Inhibitor Is Crucial to Structure , 2022 .

[11]  T. Glant,et al.  Impaired cumulus mucification and female sterility in tumor necrosis factor-induced protein-6 deficient mice , 2003, Development.

[12]  J. Sleeman,et al.  Hyaluronan--magic glue for the regulation of the immune response? , 2003, Trends in immunology.

[13]  J. Messina,et al.  In vitro adherence of lymphocytes to dermal endothelium under shear stress: implications in pathobiology and steroid therapy of acute cutaneous GVHD. , 2003, Blood.

[14]  J. Forrester,et al.  Involvement of CD44 in leukocyte trafficking at the blood‐retinal barrier , 2002, Journal of leukocyte biology.

[15]  R. Kannagi,et al.  Distinct Sulfation Requirements of Selectins Disclosed Using Cells That Support Rolling Mediated by All Three Selectins under Shear Flow , 2002, The Journal of Biological Chemistry.

[16]  E. Puré,et al.  Resolution of Lung Inflammation by CD44 , 2002, Science.

[17]  Lilly Y. W. Bourguignon,et al.  Signaling Properties of Hyaluronan Receptors* , 2002, The Journal of Biological Chemistry.

[18]  A. J. Day,et al.  Hyaluronan-binding Proteins: Tying Up the Giant* , 2002, The Journal of Biological Chemistry.

[19]  I. Otterness,et al.  Increased resistance to collagen-induced arthritis in CD44-deficient DBA/1 mice. , 2001, Arthritis and rheumatism.

[20]  K. Brown,et al.  Role of Sulfation in CD44-Mediated Hyaluronan Binding Induced by Inflammatory Mediators in Human CD14+ Peripheral Blood Monocytes1 , 2001, The Journal of Immunology.

[21]  V. Hascall,et al.  Two distinct populations of tumor necrosis factor-stimulated gene-6 protein in the extracellular matrix of expanded mouse cumulus cell-oocyte complexes. , 2001, Archives of biochemistry and biophysics.

[22]  J. Sleeman,et al.  CD44-dependent lymphoma cell dissemination: a cell surface CD44 variant, rather than standard CD44, supports in vitro lymphoma cell rolling on hyaluronic acid substrate and its in vivo accumulation in the peripheral lymph nodes. , 2001, Journal of cell science.

[23]  A. Vollmar,et al.  Low–molecular‐weight hyaluronic acid induces nuclear factor‐κB–dependent resistance against tumor necrosis factor α–mediated liver injury in mice , 2001 .

[24]  S. Matsuda,et al.  Hyaluronan activates cell motility of v-Src-transformed cells via Ras-mitogen-activated protein kinase and phosphoinositide 3-kinase-Akt in a tumor-specific manner. , 2001, Molecular biology of the cell.

[25]  T. Mak,et al.  CD44-Deficient Mice Exhibit Enhanced Hepatitis After Concanavalin A Injection: Evidence for Involvement of CD44 in Activation-Induced Cell Death1 , 2001, The Journal of Immunology.

[26]  K. Kimata,et al.  Defect in SHAP-Hyaluronan Complex Causes Severe Female Infertility , 2001, The Journal of Biological Chemistry.

[27]  M. Tammi,et al.  Hyaluronan binding by cell surface CD44. , 2000, The Journal of biological chemistry.

[28]  M. Zöller,et al.  Abrogation of Experimental Colitis Correlates with Increased Apoptosis in Mice Deficient for Cd44 Variant Exon 7 (Cd44v7) , 2000, The Journal of experimental medicine.

[29]  G. Nuki,et al.  CD44 is involved in selective leucocyte extravasation during inflammatory central nervous system disease , 1999, Immunology.

[30]  C. A. de la Motte,et al.  Mononuclear Leukocytes Preferentially Bind via CD44 to Hyaluronan on Human Intestinal Mucosal Smooth Muscle Cells after Virus Infection or Treatment with Poly(I·C)* , 1999, The Journal of Biological Chemistry.

[31]  M. Feldmann,et al.  CD44 involvement in experimental collagen-induced arthritis (CIA). , 1999, Journal of autoimmunity.

[32]  N. Ishiguro,et al.  The SHAP-HA complex in sera from patients with rheumatoid arthritis and osteoarthritis. , 1999, The Journal of rheumatology.

[33]  A. Tominaga,et al.  Cutting edge: an inducible sialidase regulates the hyaluronic acid binding ability of CD44-bearing human monocytes. , 1999, Journal of immunology.

[34]  R. Hyman,et al.  Site-specific de-N-glycosylation of CD44 can activate hyaluronan binding, and CD44 activation states show distinct threshold densities for hyaluronan binding. , 1998, Cancer research.

[35]  P. Herrlich,et al.  Activation-dependent modulation of hyaluronate-receptor expression and of hyaluronate-avidity by human monocytes. , 1998, The Journal of investigative dermatology.

[36]  C. Isacke,et al.  Hyaluronan-dependent cell migration can be blocked by a CD44 cytoplasmic domain peptide containing a phosphoserine at position 325. , 1998, Journal of cell science.

[37]  I. Stamenkovic,et al.  Glycosylation Provides Both Stimulatory and Inhibitory Effects on Cell Surface and Soluble CD44 Binding to Hyaluronan , 1998, The Journal of cell biology.

[38]  E. Balazs,et al.  The chemistry, biology and medical applications of hyaluronan and its derivatives , 1998 .

[39]  H. Degrendele,et al.  Requirement for CD44 in activated T cell extravasation into an inflammatory site. , 1997, Science.

[40]  M. Sy,et al.  Phorbol myristate acetate stimulates the dimerization of CD44 involving a cysteine in the transmembrane domain. , 1997, Journal of immunology.

[41]  R. Atkins,et al.  CD44 and hyaluronan expression in the development of experimental crescentic glomerulonephritis , 1997, Clinical and experimental immunology.

[42]  M. Burdick,et al.  Hyaluronan (HA) fragments induce chemokine gene expression in alveolar macrophages. The role of HA size and CD44. , 1996, The Journal of clinical investigation.

[43]  J. Sleeman,et al.  Regulated clustering of variant CD44 proteins increases their hyaluronate binding capacity , 1996, The Journal of cell biology.

[44]  I. Stamenkovic,et al.  Keratan Sulfate Modification of CD44 Modulates Adhesion to Hyaluronate (*) , 1996, The Journal of Biological Chemistry.

[45]  I. Stamenkovic,et al.  Glycosylation of CD44 is implicated in CD44-mediated cell adhesion to hyaluronan , 1996, The Journal of cell biology.

[46]  L. Picker,et al.  CD44 and its ligand hyaluronate mediate rolling under physiologic flow: a novel lymphocyte-endothelial cell primary adhesion pathway , 1996, The Journal of experimental medicine.

[47]  S. Kurono,et al.  Evidence for the Covalent Binding of SHAP, Heavy Chains of Inter-α-Trypsin Inhibitor, to Hyaluronan (*) , 1995, The Journal of Biological Chemistry.

[48]  K. Oritani,et al.  Glycosylation of CD44 negatively regulates its recognition of hyaluronan , 1995, The Journal of experimental medicine.

[49]  A. Perschl,et al.  Variant cell lines selected for alterations in the function of the hyaluronan receptor CD44 show differences in glycosylation , 1995, The Journal of experimental medicine.

[50]  T. Glant,et al.  Anti-CD44 treatment abrogates tissue aedema and leukocyte infiltration in murine arthrtis , 1995, Nature Medicine.

[51]  E. Puré,et al.  T lymphocytes adhere to airway smooth muscle cells via integrins and CD44 and induce smooth muscle cell DNA synthesis , 1994, The Journal of experimental medicine.

[52]  J. H. Wang,et al.  Palmitoylation of CD44 interferes with CD3-mediated signaling in human T lymphocytes. , 1994, International immunology.

[53]  L. Huang,et al.  A serum-derived hyaluronan-associated protein (SHAP) is the heavy chain of the inter alpha-trypsin inhibitor. , 1993, The Journal of biological chemistry.

[54]  L. Klampfer,et al.  TSG-6: a TNF-, IL-1-, and LPS-inducible secreted glycoprotein associated with arthritis. , 1993, Journal of immunology.

[55]  E. Puré,et al.  CD44 is necessary for optimal contact allergic responses but is not required for normal leukocyte extravasation , 1993, The Journal of experimental medicine.

[56]  P. Kincade,et al.  CD44 and its interaction with extracellular matrix. , 1993, Advances in immunology.

[57]  U. Günthert,et al.  Current Topics in Microbiology and Immunology (1993) Volume on Adhesion in Leukocyte Homing and Differentiation (eds D. Dunon, C. R. Mackay, and B. A. Imhof) CD44: a multitude of isoforms with diverse functions , 2007 .

[58]  A. Brass,et al.  Secondary and tertiary structures of hyaluronan in aqueous solution, investigated by rotary shadowing-electron microscopy and computer simulation. Hyaluronan is a very efficient network-forming polymer. , 1991, The Biochemical journal.

[59]  J. Enghild,et al.  Chondroitin 4-sulfate covalently cross-links the chains of the human blood protein pre-alpha-inhibitor. , 1991, The Journal of biological chemistry.

[60]  S. Suzuki,et al.  Hyaluronic acid associated with the surfaces of cultured fibroblasts is linked to a serum-derived 85-kDa protein. , 1990, The Journal of biological chemistry.

[61]  Brian Seed,et al.  A lymphocyte molecule implicated in lymph node homing is a member of the cartilage link protein family , 1989, Cell.

[62]  D. Heinegård,et al.  Cartilage proteoglycans. Assembly with hyaluronate and link protein as studied by electron microscopy. , 1988, The Biochemical journal.

[63]  Larry V. McIntire,et al.  Effect of flow on polymorphonuclear leukocyte/endothelial cell adhesion , 1987 .