Salt-Sensitive Increase of Macrophages in the Kidneys of Dahl SS Rats.

Abstract

Studies of Dahl Salt-Sensitive (SS) rats have shown that renal CD3+ T-cells and ED-1+ macrophages are involved in the development of SS hypertension and renal damage. The present study demonstrated that the increase in renal immune cells, which accompanies renal hypertrophy and albuminuria in high salt-fed Dahl SS rats, is absent in Sprague Dawley and SSBN13 rats that are protected from the SS disease phenotype. Flow cytometric analysis demonstrated that >70% of the immune cells in the SS kidney are M1 macrophages. PCR profiling of renal myeloid cells showed a salt-induced upregulation in 9 of 84 genes related to Toll-Like Receptor signaling, with notable upregulation of the TLR4/CD14/MD2 complex. Due to the prominent increase in macrophages in the SS kidney, we used liposome-encapsulated clodronate to deplete macrophages and assess their contribution to SS hypertension and renal damage. Dahl SS animals were administered either Clodronate-Liposomes (Clod-Lipo), Clodronate (Clod), or PBS-Liposomes (PBS-Lipo) as a vehicle control. Clod-Lipo treatment depleted circulating and splenic macrophages by approximately 50%; however, contrary to our hypothesis, Clod-Lipo-treated animals developed an exacerbated SS response in respect to blood pressure and albuminuria, accompanied by increased renal T- and B-cells. Interestingly, those treated with Clod also demonstrated an exacerbated phenotype, but it was less severe than Clod-Lipo-treated animals and independent of changes to the number of renal immune cells. Here, we have shown that renal macrophages in Dahl SS animals sustain a M1 pro-inflammatory phenotype in response to increased dietary salt and highlighted potential adverse effects of clodronate-liposome macrophage depletion.