Sodium Chloride Induces Human Tubular Epithelial Cell CCL26 Expression That Associates With Monocyte Accumulation in the Human Kidney
- Pathology and Lab Medicine
November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Pathology and Lab Medicine
- 1700 Pathology and Lab Medicine
- Schmitz, Jessica, Medizinische Hochschule Hannover, Hannover, Niedersachsen, Germany
- Brauns, Nicolas, Medizinische Hochschule Hannover, Hannover, Niedersachsen, Germany
- Breloh, Anne M., Medizinische Hochschule Hannover, Hannover, Niedersachsen, Germany
- Braesen, Jan H., Medizinische Hochschule Hannover, Hannover, Niedersachsen, Germany
- Haller, Hermann G., Medizinische Hochschule Hannover, Hannover, Niedersachsen, Germany
- Von Vietinghoff, Sibylle, Universitatsklinikum Bonn, Bonn, Germany
Renal immune cells serve as sentinels against ascending bacteria but also promote detrimental inflammation. The kidney medulla is characterized by extreme electrolyte concentrations. We here address how its main osmolytes, NaCl and urea, regulate tubular cell cytokine expression and monocyte chemotaxis.
Immunohistology was performed in human kidney sections, human monocyte function and tubular cell cytokine production was analyzed in cell culture.
In the healthy human kidney, more monocytes were detected in medulla than cortex. The monocyte gradient was attenuated in patients with medullary NaCl depletion by loop diuretic therapy and in the nephrotic syndrome. Renal tubular epithelial cell gene expression responded similarly to NaCl and tonicity control mannitol, but not urea. NaCl significantly upregulated chemotactic cytokines, most markedly CCL26, CCL2 and CSF1. This induction was inhibited by ROS scavenger n-acetylcysteine. In contrast urea, the main medullary osmolyte in catabolism, dampened tubular epithelial CCL26 and CSF1 expression. Renal medullary chemokine and monocyte marker expression decreased in catabolic mice. NaCl-, but not urea-stimulated tubular epithelium or CCL2 and CCL26 promoted human classical monocyte migration. CCL26 improved bactericidal function. In the human kidney medulla, monocyte densities correlated with tubular CCL26 protein abundance.
Medullary-range NaCl, but not urea, promotes tubular cytokine expression and monocyte recruitment. Our results delineate CCL26 expression in the kidney and determine its antibacterial function. This may contribute to the pyelonephritis vulnerability in catabolism but can possibly be harnessed against pathologic inflammation.