Cloning of an alternate form of vascular cell adhesion molecule-1 (VCAM1)

C Hession1, R Tizard, C Vassallo

  • 1Biogen, Inc., Cambridge, Massachusetts 02142.

Insights

Researchers discovered a longer form of Vascular Cell Adhesion Molecule-1 (VCAM1) in human endothelial cells. This longer VCAM1, alongside the original form, plays a role in leukocyte adhesion during inflammation.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Vascular Cell Adhesion Molecule-1 (VCAM1) is an Ig superfamily member.
  • VCAM1 is induced by inflammatory cytokines like IL-1 and TNF on HUVECs.
  • VCAM1 mediates mononuclear leukocyte binding via integrin VLA-4.

Purpose of the Study:

  • To clone and characterize a novel human VCAM1 variant.
  • To investigate the expression and prevalence of different VCAM1 forms.
  • To determine the functional significance of VCAM1 isoforms in cell adhesion.

Main Methods:

  • Cloning and expression of VCAM1 cDNA.
  • mRNA characterization from HUVECs post-cytokine induction.
  • Immunoprecipitation and deglycosylation of VCAM1 protein.
  • Functional adhesion assays with VLA-4 expressing cell lines.

Main Results:

  • A new, longer human VCAM1 isoform with an additional Ig-like domain was identified.
  • Both long and short VCAM1 mRNAs are expressed in HUVECs, with the long form predominating.
  • The long VCAM1 form is the major protein expressed on endothelium.
  • Both VCAM1 forms support the adhesion of VLA-4 expressing cells.

Conclusions:

  • The novel VCAM1 isoform arises from alternative mRNA splicing.
  • Both VCAM1 forms contribute to VLA-4 mediated leukocyte adhesion.
  • Understanding VCAM1 isoforms is crucial for inflammatory and immune response research.

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