Sialylation of ICAM-2 on platelets impairs adhesion of leukocytes via LFA-1 and DC-SIGN.
Intercellular adhesion molecule (ICAM)-2 is highly expressed on platelets and endothelium and is a counter-receptor for the leukocyte integrin, lymphocyte function-associated antigen-1 (LFA-1) and for the dendritic cell-specific, ICAM-grabbing non-integrin (DC-SIGN) protein. In this study, we investigated structural and functional differences between ICAM-2 from platelets and that from endothelial cells. The isoelectric point (pI) of ICAM-2 from HUVEC was pH 3.5-4.3, whereas that of platelet ICAM-2 was more acidic at pH 3.0-3.7. This charge difference was abolished by treatment with N-glycanase or neuraminidase, thus it was due to cell-specific N-linked glycosylation. Purified, immobilized platelet ICAM-2 supported 50% less adhesion of LFA-1-bearing T cells than did purified HUVEC ICAM-2 and no adhesion was observed of monocyte-derived immature dendritic cells via DC-SIGN to platelet ICAM-2. Treatment of platelet ICAM-2 with neuraminidase abolished these functional differences. These findings demonstrated that physiologic sialylation of platelet ICAM-2 renders it less able than endothelial ICAM-2 to support adherence of leukocytes.
Weber
Kim S C
KS
Department of Medicine, Division of Rheumatology, Immunology & Allergy, Harvard Medical School, Boston, Massachusetts, USA.
Alon
Ronen
R
Klickstein
Lloyd B
LB
D015703:Antigens, CD / Q000378:metabolism* / Q000502:physiology; D001792:Blood Platelets / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000378:metabolism* / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D037181:Lectins, C-Type / Q000502:physiology*; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000502:physiology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D016169:Lymphocyte Function-Associated Antigen-1; D019158:N-Acetylneuraminic Acid; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C065289:ICAM2 protein, human