CD8+ T cells stimulate Na-Cl co-transporter NCC in distal convoluted tubules leading to salt-sensitive hypertension.

Recent studies suggest a role for T lymphocytes in hypertension. However, whether T cells contribute to renal sodium retention and salt-sensitive hypertension is unknown. Here we demonstrate that T cells infiltrate into the kidney of salt-sensitive hypertensive animals. In particular, CD8+ T cells directly contact the distal convoluted tubule (DCT) in the kidneys of DOCA-salt mice and CD8+ T cell-injected mice, leading to up-regulation of the Na-Cl co-transporter NCC, p-NCC and the development of salt-sensitive hypertension. Co-culture with CD8+ T cells upregulates NCC in mouse DCT cells via ROS-induced activation of Src kinase, up-regulation of the K+ channel Kir4.1, and stimulation of the Cl- channel ClC-K. The last event increases chloride efflux, leading to compensatory chloride influx via NCC activation at the cost of increasing sodium retention. Collectively, these findings provide a mechanism for adaptive immunity involvement in the kidney defect in sodium handling and the pathogenesis of salt-sensitive hypertension.

Prostaglandins produced during class A scavenger receptor-mediated macrophage adhesion differentially regulate cytokine production.

Inflammation is associated with modification of the extracellular environment, changes in cytokine expression, and the accumulation of immune cells. Such modifications create ligands that support SR-A-mediated macrophage adhesion and retention. This may be particularly important in settings, such as atherosclerosis and diabetes, as modified lipoproteins and gluc-collagen are ligands for SR-A. SR-A-mediated adhesion requires the PLA2-dependent generation of AA and its metabolism by 12/15 LOX. In contrast, the inhibition of the COX-dependent conversion of AA to PG had no effect on SR-A-mediated adhesion. In this study, macrophages were isolated from SR-A+/+ and SR-A-/- mice and plated on gluc-collagen to test the hypothesis that COX-derived PGs are produced during SR-A-mediated adhesion and regulate macrophage function. SR-A-mediated binding to gluc-collagen induced a rapid but transient increase in PG production, which required the activation of PLA2 and Src kinase but not PI3K. SR-A+/+ macrophages cultured on gluc-collagen for 24 h secreted a similar amount of TNF-α and 2.5-fold more IL-10 than SR-A-/- macrophages. The inhibition of COX substantially increased TNF-α production but reduced IL-10 levels in SR-A+/+ macrophages. These effects of COX inhibition were reversed by exogenous PGE2 and mimicked by specific antagonism of the EP4 receptor. Thus, in addition to the enhancement of macrophage adhesion, SR-A binding to gluc-collagen stimulates PG production, which in turn, differentially regulates the expression of inflammatory cytokines.

[Experimental study on processing of Paeonia lactiflora].

OBJECTIVE: To provide experimental data for the quality control of processed Paeonia lactiflora, a Chinese herbal medicine. METHOD: Traditional processing of P. lactiflora was simulated, content of paeoniflorin and water extracts among different preparations were assayed by HPLC; The quantitative correlations among different processing conditions were analyzed, the effects of processing parameters on the contents of paeoniflorin and water extracts were assayed a nanalysed. RESULT AND CONCLUSION: The controlled processing parameters were correlated with covariables which showed that processing procedures was controllable, and the heating temperature was a factor impacting the content of paeoniflorin.