Characterization of apoptotic macrophages in atheromatous tissue of humans and heritable hyperlipidemic rabbits

R Kinscherf1, M Wagner, H Kamencic

  • 1Department of Anatomy and Cell Biology III, University of Heidelberg, Germany. Ralf.Kinscherf@urz.uni-heidelberg.de

Atherosclerosis
|June 25, 1999
PubMed

Insights

Apoptotic macrophages in atherosclerosis are activated, oxidatively stressed, and express integrins, suggesting these factors accelerate their programmed cell death within lesions.

Area of Science:

  • Cardiovascular Biology
  • Immunology
  • Cellular Pathology

Background:

  • Apoptotic macrophages are prevalent in atherosclerotic plaques, indicating programmed cell death's role in disease regulation.
  • Understanding the characteristics of these apoptotic macrophages is crucial for elucidating atherosclerosis pathogenesis.

Purpose of the Study:

  • To comprehensively characterize apoptotic macrophages within human and heritable hyperlipidemic (HHL) rabbit atherosclerotic lesions.
  • To investigate the molecular markers and cellular states associated with macrophage apoptosis in atherosclerosis.

Main Methods:

  • Immunohistochemical analysis of human carotid/aortic and HHL rabbit aortic tissues using antibodies against CD11b/CD18, CD44, MHC class I/II, iNOS, MnSOD, TNFα, p53, c-jun/AP-1, RAM-11.
  • TUNEL (TdT-mediated dUTP nick end labeling) technique to identify apoptotic cells.
  • Computer-assisted morphometric analysis for quantitative correlation studies.

Main Results:

  • Apoptotic macrophages in human and HHL rabbit lesions exhibited co-localization with markers for MnSOD, alphaMbeta2-integrin, CD44, MHC class I/II, iNOS, TNFα, and p53.
  • Morphometric analysis revealed positive correlations between MnSOD-immunoreactive macrophages and alphaMbeta2-integrin/CD44-immunoreactive macrophages.
  • No significant correlation was found between MnSOD-immunoreactive macrophages and MHC class I/II or RAM-11-immunoreactive macrophages.

Conclusions:

  • Apoptotic macrophages in atherosclerotic lesions are characterized as activated, antigen-presenting, integrin-expressing, and oxidatively stressed.
  • These cellular states, known to induce apoptosis in vitro, likely contribute to the susceptibility of macrophages to programmed cell death within atherosclerotic lesions.
  • The findings highlight the complex role of macrophage apoptosis in the progression of atherosclerosis.