Cleavage of membrane-associated ICAM-1 from astrocytes: involvement of a metalloprotease

Glia. 1998 Feb;22(2):103-12. doi: 10.1002/(sici)1098-1136(199802)22:2<103::aid-glia1>;2-8.


Disease of the central nervous system (CNS) with immune-mediated pathogenesis is frequently associated with enhanced expression of intercellular adhesion molecule-1 (ICAM-1) on resident glial cells, including astrocytes. Recently, a soluble form of ICAM-1 (sICAM-1) has been demonstrated within the CNS and cerebrospinal fluid (CSF), arising from an intrathecal source. In this study, we investigated the ability of TNF-alpha treated astrocytes to generate sICAM-1 from a population of membrane-associated ICAM-1. To determine the ability of ICAM-1 to be released from the cell surface, generating sICAM-1, cell cultures were treated with TNF-alpha for 21 h prior to cell surface protein iodination or biotinylation. We show that the membrane-associated form of ICAM-1 (approximately 90 KD) is converted to a soluble form (approximately 83 KD) in cell culture supernatants. The half-life of TNF-alpha induced membrane-associated ICAM-1 on rat astrocytes is approximately 5 h. The proteolytic cleavage process for the conversion of membrane-associated ICAM-1 to sICAM-1 was sensitive to Batimastat (BB94) and phosphoramidon, two inhibitors of metalloproteases, whereas inhibitors of serine-, cysteine-, aspartic-, and chymotrypsin-like proteases had no effect on this process. These results indicate that astrocytes can be induced to produce sICAM-1, and this process involves a metalloprotease that is induced/activated in a TNF-alpha-dependent fashion. It is proposed that astrocytes may be a source of intrathecal sICAM-1 under inflammatory conditions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Astrocytes / enzymology*
  • Biotin / metabolism
  • Blotting, Western
  • Cell Membrane / enzymology
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Half-Life
  • Indicators and Reagents
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Kinetics
  • Metalloendopeptidases / metabolism*
  • Neuroglia / enzymology
  • Neuroglia / metabolism
  • Precipitin Tests
  • Protease Inhibitors / pharmacology
  • Rats
  • Transforming Growth Factor beta / pharmacology


  • Indicators and Reagents
  • Protease Inhibitors
  • Transforming Growth Factor beta
  • Intercellular Adhesion Molecule-1
  • Biotin
  • Metalloendopeptidases