Senescent CD14+CD16+ monocytes exhibit proinflammatory and proatherosclerotic activity

Area of Science:

• Immunology
• Cell Biology
• Gerontology

Background:

• Elderly individuals and patients with chronic inflammatory diseases exhibit an increased CD14(+)CD16(+) monocyte subset.
• The origin and functional significance of this monocyte subset remain incompletely understood.

Purpose of the Study:

• To investigate if prolonged survival of CD14(++)CD16(-) monocytes leads to cellular senescence.
• To analyze the molecular, phenotypic, and functional characteristics of these senescent monocytes.

Main Methods:

• An in vitro model was used to extend the lifespan of healthy monocytes.
• Assessed cell senescence markers (telomere length, β-galactosidase activity), intracellular cytokine expression, endothelial cell interaction, and antigen-presenting cell (APC) activity.

Main Results:

• CD14(+)CD16(+) monocytes displayed senescence markers, including shortened telomeres and increased β-galactosidase activity compared to CD14(++)CD16(-) cells.
• These senescent monocytes showed features of activation, such as CD209 expression, cytokine release, enhanced lymphocyte proliferation support, elevated chemokine receptor expression, and increased adhesion to endothelial cells.

Conclusions:

• Senescent CD14(+)CD16(+) monocytes are activated cells with heightened inflammatory potential and endothelial cell interaction capabilities.
• The accumulation of these senescent monocytes may partially explain chronic inflammation and atherosclerosis development in aging populations and patients with chronic inflammatory conditions.