Inflammatory environment and oxidized LDL convert circulating human proangiogenic cells into functional...

Area of Science:

• Immunology
• Cell Biology
• Vascular Biology

Background:

• Human circulating Progenitor cells (PACs) have well-defined functions, but their behavior in inflammatory vascular environments is less understood.
• Vascular inflammation is a key factor in diseases like atherosclerosis, involving factors like oxidized LDL (oxLDL).

Purpose of the Study:

• To investigate how inflammatory stimuli, specifically pro-inflammatory cytokines and oxLDL, alter the phenotype and function of human PACs.
• To test the hypothesis that these stimuli convert PACs into immune-modulating or pro-inflammatory cells.

Main Methods:

• PACs were derived from peripheral blood mononuclear cells (PBMCs) and cultured.
• Cells were exposed to pro-inflammatory cytokines (APCcy) or oxLDL (APCox).
• Phenotypic analysis involved secretome and whole genome transcriptome profiling, alongside expression of maturation markers (CD80, CD83, CD86) and T cell proliferation assays (BrdU incorporation).

Main Results:

• PACs converted into Antigen-Presenting Cells (APCs) expressing maturation markers CD80, CD83, and CD86.
• Both cytokine-exposed (APCcy) and oxLDL-exposed (APCox) cells induced robust T cell proliferation.
• Despite similar lymphocyte activation, APCcy and APCox exhibited distinct secretory pathways, mRNA expression profiles, and gene clusters, suggesting different antigen processing functions.

Conclusions:

• Pro-inflammatory cytokines and oxLDL transform human PACs into APCs with potent lymphocyte-activating capabilities.
• The specific inflammatory trigger influences the degree of APC maturation and their paracrine functions.
• Functional genomics reveals distinct pathways in APCcy versus APCox, impacting their roles in immune responses.