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Quantification of Monocyte Transmigration and Foam Cell Formation from Individuals with Chronic Inflammatory Conditions
Published on: October 17, 2017
Variable expression of human myeloid specific nuclear antigen MNDA in monocyte lineage cells in atherosclerosis
Robert C Briggs1, James B Atkinson, Roberto N Miranda
1Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA. bob.briggs@mcmail.vanderbilt.edu
Abstract:
MNDA (human myeloid nuclear differentiation antigen) is expressed in specific lineages of hematopoietic cells and most notably at high levels in macrophages at sites of inflammation. MNDA and related proteins appear to modulate the activity of transcription factors and in some cases have a role in mediating cell death. The expression of MNDA was characterized in normal and diseased human aorta. MNDA positive cells double labeled for CD68 in all tissue examined. Twenty percent of normal aortas were negative or contained rare MNDA positive cells while other normal aorta contained more frequent positive cells. In atherosclerotic aorta, the number of MNDA positive cells increased with progression of disease. In normal and early lesions, MNDA positive cells adjacent to the endothelium generally displayed a strong MNDA reactivity associated with small amount of CD68 reactive cytoplasm. In the same sections, MNDA positive cells at increasing distances from the endothelium displayed lower MNDA reactivity and were associated with larger amounts of CD68 reactive cytoplasm. Foam cells in fatty streaks exhibited MNDA reactivity that ranged from strong to weak or negative. In advanced lesions, cells in the shoulder and those in fibrous tissue surrounding an atheroma were highly reactive for MNDA. However, only a fraction of the CD68 positive foam cells near the lipid core under the cap and shoulder contained MNDA reactivity. The variation in MNDA expression appeared to change with phenotypic specialization of monocytes in atherosclerosis consistent with its association with inflammation and suspected roles in regulating gene expression or in mediating cell death.
Insights
Human myeloid nuclear differentiation antigen (MNDA) expression increases in macrophages during atherosclerosis progression. MNDA levels vary with cell specialization, suggesting roles in inflammation and cell death within diseased aorta.
Area of Science:
- Immunology
- Cell Biology
- Pathology
Background:
- Human myeloid nuclear differentiation antigen (MNDA) is found in hematopoietic cells, particularly macrophages at inflammation sites.
- MNDA and related proteins may regulate transcription factors and mediate cell death.
Purpose of the Study:
- To characterize MNDA expression in normal and diseased human aorta.
- To investigate the relationship between MNDA expression and macrophage phenotype in atherosclerosis.
Main Methods:
- Immunohistochemical analysis of MNDA and CD68 expression in human aorta tissues.
- Correlation of MNDA reactivity with disease progression and cell morphology.
Main Results:
- MNDA-positive cells were identified and co-localized with CD68 in all examined tissues.
- MNDA expression increased with atherosclerosis progression, varying with cell location and disease stage.
- Foam cells showed variable MNDA reactivity, with higher expression in advanced lesions.
Conclusions:
- MNDA expression in aortic macrophages changes with disease progression and cellular specialization.
- MNDA's variable expression pattern suggests a role in the inflammatory processes of atherosclerosis.
