Abstract
Excessive NaCl intake is associated with a variety of fibrosing diseases such as renal and cardiac fibrosis. This association has been attributed to increased blood pressure as the result of high NaCl intake. However, studies in patients with high NaCl intake and fibrosis reveal a connection between NaCl intake and fibrosis that is independent of blood pressure. We find that increasing the extracellular concentration of NaCl to levels that may occur in human blood after high-salt intake can potentiate, in serum-free culture conditions, the differentiation of freshly-isolated human monocytes into fibroblast-like cells called fibrocytes. NaCl affects the monocytes directly during their adhesion. Potassium chloride and sodium nitrate also potentiate fibrocyte differentiation. The plasma protein Serum Amyloid P (SAP) inhibits fibrocyte differentiation. High levels of extracellular NaCl change the SAP Hill coefficient from 1.7 to 0.8, and cause a four-fold increase in the concentration of SAP needed to inhibit fibrocyte differentiation by 95%. Together, our data suggest that NaCl potentiates fibrocyte differentiation. NaCl-increased fibrocyte differentiation may thus contribute to NaCl-increased renal and cardiac fibrosis.
Highlights
Fibrosing diseases such as pulmonary fibrosis, congestive heart disease, and renal fibrosis involve the formation of unwanted scar tissue in internal organs [1,2]
Additional NaCl can potentiate fibrocyte formation without influencing cell viability Since fibrocytes are implicated in fibrosing diseases, and NaCl may promote fibrosis, we examined the hypothesis that NaCl might affect fibrocyte differentiation
In RPMI 1640 medium, NaCl caused a maximum potentiation of fibrocyte differentiation at 20 mM additional NaCl, making [Na+] = 154 mM, and [Cl2] = 127 mM, again in excess when compared to human blood
Summary
Fibrosing diseases such as pulmonary fibrosis, congestive heart disease, and renal fibrosis involve the formation of unwanted scar tissue in internal organs [1,2]. Fibrosis involves infiltration of blood leukocytes into the affected organs, activation and/or appearance of fibroblast-like cells, tissue remodeling, and deposition of extracellular matrix proteins such as collagen [3,4,5,6,7,8]. Fibrocytes are CD45+, collagen I+ fibroblast-like cells that have been implicated in scar tissue formation and fibrosis [3,5,6,8,9]. These cells share similarities with both blood leukocytes and tissue resident cells [7,9]. Serum Amyloid P (SAP), a pentameric protein from the pentraxin family of proteins, interacts with Fc receptors on monocytes to inhibit fibrocyte differentiation [13,14,15,16]
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