Variable expression of human myeloid specific nuclear antigen MNDA in monocyte lineage cells in atherosclerosis

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.

Activation of a TGF-β-Specific Multistep Gene Expression Program in Mature Macrophages Requires Glucocorticoid-Mediated Surface Expression of TGF-β Receptor II

“…Transcription regulators ELL2, TLE3, and BCoR also up-regulated by TGF-␤ were implicated in the maintenance of undifferentiated cell states and in suppression of apoptosis (49 -51). Transcription factors that belong to the group of late TGF-␤ response genes in M2 macrophages include another AP-1 family member, FOS (27), and human myeloid nuclear differentiation Ag implicated in inflammatory reactions and apoptosis and present in macrophages in atherosclerotic plaques (52,53). We conclude that these transcription factors together with the R-Smads are responsible for the development of the macrophage phenotype observed after stimulation of M2 IL-4/GC by TGF-␤.…”

Transcriptional Profiling of Human Monocytes Identifies the Inhibitory Receptor CD300a as Regulator of Transendothelial Migration

“…These include members of the NR4A nuclear hormone receptor subfamily, NR4A2 and NR4A3, which are known to modulate inflammatory responses [29], and the human myeloid nuclear differentiation antigen (MNDA) [30]. The latter had been implicated in myeloid cell differentiation, although its functional role in this process is unclear [31].…”

Dysregulated Human Myeloid Nuclear Differentiation Antigen Expression in Myelodysplastic Syndromes: Evidence for a Role in Apoptosis

“…The MNDA rat monoclonal antibody 3C1 was used in previous studies to document cell-specific expression (14)(15)(16)(17)(18)(19) and was also used to immunoaffinity purify MNDA for sequence analysis (20). The monoclonal antibody 3C1 (Chemicon International, Inc. Temecula, CA) was used in all immunochemical assays of MNDA expression.…”