High Salt Activates Human Monocytes and Promotes their Conversion into Dendritic Cells via Formation of Immunogenic Isoketal‐adducts

• DOI: 10.1096/fasebj.30.1_supplement.1216.4
• Publication Date: 2023-11-26T16:34:18Z
• Authors: Annet Kirabo; Natalia Barbaro; Jason David Foss; Kim Ramil Montaniel; Wei Chen; David Glenn Harrison
• Keywords: CD86

High blood pressure is a major modifiable risk factor for cardiovascular disease (CVD) which the leading cause of death worldwide. Excessive salt intake and inflammation are implicated in genesis hypertension. It has recently become evident that sodium accumulates interstitial space can promote through poorly defined mechanisms. We published new pathway increased oxidative stress dendritic cells (DCs) leads to formation isoketal‐modified proteins act as neo‐antigens activate T cells. hypothesized increasing chloride (NaCl) excess physiological concentrations activates antigen presenting via immunogenic isoketals. exposed monocytes from human volunteers normal NaCl (150 mM/L), elevated (190 or an equiosmoloar concentration mannitol. found exposure high salt, but not mannitol, caused 2‐fold increase proteins. This was associated with activation marker CD86 (466 ± 192 vs 596 324 salt) production inflammatory cytokines IL‐6, IL‐β TNF‐α. Interestingly, these expressed surface markers indicative transformation DCs, evidenced by their acquisition CD83. In additional immunofluorescence studies, we 7 days acquire DC like morphology. Moreover, using flow cytometry, confirmed causes lose monocyte CD14, gain CD209. When co‐cultured same patients, drive cell proliferation. Scavenging isoketals during prevented conversion into DCs ability Thus, have novel whereby lead due These observations provide insight how environments state. Support Funding Information work supported National Institutes Health grants R01HL039006, P01HL058000, P01HL095070, P01GM015431, R01HL108701, R01HL105294, VITA award HHSN268201400010C Strategically Focused Research Network Award American Heart Association.