Related Experiment Video
Updated: Jun 23, 2026
Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
Absence of p21Waf1/Cip1/Sdi1 modulates macrophage differentiation and inflammatory response and protects against
Aksam J Merched1, Lawrence Chan
1Department of Molecular, Division of Diabetes, Endocrinology, and Metabolism, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. amerched@bcm.tmc.edu
Background:
The tumor suppressor p53 protects against atherosclerosis progression in several different mouse models. A major target of p53 is p21, the cyclin-dependent kinase inhibitor that regulates entry into the cell cycle of different types of cells, including stem cells. p21 is also involved in the maturation and differentiation of monocytes into macrophages.
Methods And Results:
We studied the effect of p21Waf1 inactivation on atherosclerosis development in apolipoprotein E-deficient mice (apoE-/-). Contrary to previous data suggesting a protective role for p21, we found that absence of p21, either globally or in bone marrow-derived cells, protects against atherosclerosis. Atherosclerotic lesions of p21-/-/apoE-/- mice exhibit a more stable phenotype, with increased apoptosis and reduced inflammatory vascular cell adhesion molecule-1 immunostaining but no difference in cellular proliferation compared with lesions of p21+/+/apoE-/- mice. Because bone marrow-derived cells mediate many of the effects of p21, we examined the expression profile of 23 genes in macrophages using real-time polymerase chain reaction. Compared with their p21+/+ counterparts, peritoneal macrophages of p21-/- mice express lower levels of proinflammatory markers, including macrophage inflammatory proteins 1 and 2 and interleukin-1alpha, and higher levels of putative protective genes, such as scavenger receptor type B-I and LDL receptor-related protein. Furthermore, we found that, in comparison with p21+/+ macrophages, p21-/- macrophages displayed increased phagocytic activity toward fluorescent latex microspheres as well as apoptotic cells, thus uncovering a novel mechanism of the antiinflammatory activity of p21-/- macrophages.
Conclusions:
Loss of p21 protects against atherosclerosis in apoE-/- mice. The data underscore the important role of p21 in macrophage function and inflammation and provide insight into the mechanism of the proatherogenic effect of p21.
Insights
Loss of p21 protects against atherosclerosis. Absence of p21 in bone marrow cells reduces inflammation and enhances macrophage function, revealing a novel anti-inflammatory mechanism.
Area of Science:
- Cardiovascular Biology
- Molecular Biology
- Immunology
Background:
- The tumor suppressor p53 plays a role in preventing atherosclerosis.
- p53 targets p21, a cyclin-dependent kinase inhibitor crucial for cell cycle regulation and macrophage differentiation.
- p21's role in atherosclerosis has been debated, with some studies suggesting a protective function.
Purpose of the Study:
- To investigate the effect of p21 inactivation on atherosclerosis development in apolipoprotein E-deficient (apoE-/-) mice.
- To elucidate the mechanisms underlying p21's influence on macrophage function and vascular inflammation.
Main Methods:
- Atherosclerosis development was studied in p21-/-/apoE-/- mice and compared to p21+/+/apoE-/- controls.
- Gene expression profiles of macrophages were analyzed using real-time polymerase chain reaction.
- Macrophage phagocytic activity was assessed using latex microspheres and apoptotic cells.
Main Results:
- Absence of p21 protected against atherosclerosis, leading to more stable atherosclerotic lesions.
- p21 deficiency resulted in increased apoptosis and reduced expression of inflammatory markers in lesions.
- p21-deficient macrophages showed reduced pro-inflammatory gene expression and enhanced phagocytic capacity.
Conclusions:
- Loss of p21 confers protection against atherosclerosis in apoE-/- mice.
- p21 significantly influences macrophage function and inflammation.
- The study reveals a novel pro-atherogenic role for p21 in macrophages.
Related Concept Videos
01:38Inflammation
02:23Abnormal Proliferation