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-alpha-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 IalphaI, 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.
Zhuo
Lisheng
L
Institute for Molecular Science of Medicine, Aichi Medical University, Nagakute, Aichi 480-1195, Japan.
Kanamori
Akiko
A
Kannagi
Reiji
R
Itano
Naoki
N
Wu
Jiwen
J
Hamaguchi
Michinari
M
Ishiguro
Naoki
N
Kimata
Koji
K
D000510:Alpha-Globulins / Q000378:metabolism*; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000473:pathology; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D018960:Hyaluronan Receptors / Q000502:physiology*; D006820:Hyaluronic Acid / Q000502:physiology*; D019169:Jurkat Cells; D007700:Kinetics; D007962:Leukocytes / Q000502:physiology*; D008223:Lymphoma; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000378:metabolism; D033081:Shear Strength; D012878:Skin Neoplasms; D013583:Synovial Membrane / Q000473:pathology
D000510:Alpha-Globulins; D018960:Hyaluronan Receptors; D011994:Recombinant Proteins; C011877:inter-alpha-inhibitor; D006820:Hyaluronic Acid