Constitutive expression and enzymatic cleavage of ICAM-1 in the spontaneously hypertensive rat

J Vasc Res. 2011;48(5):386-96. doi: 10.1159/000323474. Epub 2011 Apr 4.

Abstract

Background/aims: Leukocyte adhesion to the endothelium is abnormal in hypertension. We have recently shown that spontaneously hypertensive rats (SHRs) have circulating leukocytes with enhanced CD18 receptor cleavage. In the current study, we investigate expression levels of its counter receptor, intercellular adhesion molecule (ICAM-1), and its possible proteolytic cleavage in the SHR and control Wistar rat.

Methods: ICAM-1 was labeled on tissue sections with two antibodies targeting its extracellular and intracellular domains and evaluated by light absorption measurements. The in situ cleavage of ICAM-1 was assessed by treating vessel sections with matrix metalloproteinase (MMP)-7, MMP-9 and elastase.

Results: SHRs showed a significant increase in ICAM-1 expression in liver and kidney compared with Wistar rats. The liver and kidney glomeruli exhibit a discrepancy in label density between intra- and extracellular antibodies, which suggests that enzymatic cleavage may be a factor determining ICAM-1 distribution. MMP-7 and MMP-9, which are elevated in SHR plasma, and elastase, which has elevated activity in SHR neutrophils, cleave the extracellular domain of ICAM-1 when applied to the tissue.

Conclusion: ICAM-1 expression in SHRs is upregulated in a tissue-specific manner. Proteolytic cleavage of the extracellular domain of ICAM-1 and accumulation in kidney glomeruli may play a role in the renal involvement of inflammation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Hypertension / metabolism*
  • Immunohistochemistry / methods
  • Intercellular Adhesion Molecule-1 / biosynthesis*
  • Intercellular Adhesion Molecule-1 / chemistry
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Kidney / enzymology*
  • Liver / enzymology*
  • Male
  • Matrix Metalloproteinase 7 / metabolism
  • Matrix Metalloproteinase 7 / pharmacology
  • Matrix Metalloproteinase 9 / metabolism
  • Matrix Metalloproteinase 9 / pharmacology
  • Models, Biological
  • Pancreatic Elastase / metabolism
  • Pancreatic Elastase / pharmacology
  • Protein Structure, Tertiary / physiology
  • Rats
  • Rats, Inbred SHR
  • Rats, Wistar
  • Species Specificity

Substances

  • Intercellular Adhesion Molecule-1
  • Pancreatic Elastase
  • Matrix Metalloproteinase 7
  • Matrix Metalloproteinase 9