Angiotensin-converting enzyme (ACE) inhibitors are widely used to reduce blood pressure. Here, we examined if an ACE is important for the antibacterial effectiveness of neutrophils. ACE knockout mice or mice treated with an ACE inhibitor were more susceptible to bacterial infection by methicillin-resistant (MRSA). In contrast, mice overexpressing ACE in neutrophils (Neu mice) have increased resistance to MRSA and better in vitro killing of MRSA, , and ACE overexpression increased neutrophil production of reactive oxygen species (ROS) following MRSA challenge, an effect independent of the angiotensin II AT1 receptor. Specifically, as compared with wild-type (WT) mice, there was a marked increase of superoxide generation (>twofold, < .0005) in Neu neutrophils following infection, whereas ACE knockout neutrophils decreased superoxide production. Analysis of membrane p47-phox and p67-phox indicates that ACE increases reduced NAD phosphate oxidase activity but does not increase expression of these subunits. Increased ROS generation mediates the enhanced bacterial resistance of Neu mice because the enhanced resistance is lost with DPI (an inhibitor of ROS production by flavoenzymes) inhibition. Neu granulocytes also have increased neutrophil extracellular trap formation and interleukin-1β release in response to MRSA. In a mouse model of chemotherapy-induced neutrophil depletion, transfusion of ACE-overexpressing neutrophils was superior to WT neutrophils in treating MRSA infection. These data indicate a previously unknown function of ACE in neutrophil antibacterial defenses and suggest caution in the treatment of certain individuals with ACE inhibitors. ACE overexpression in neutrophils may be useful in boosting the immune response to antibiotic-resistant bacterial infection.

The SET domain-containing protein, pTAC14, was previously identified as a component of the transcriptionally active chromosome (TAC) complexes. Here, we investigated the function of pTAC14 in the regulation of plastid-encoded bacterialtype RNA polymerase (PEP) activity and chloroplast development. The knockout of pTAC14 led to the blockage of thylakoid formation in Arabidopsis (Arabidopsis thaliana), and ptac14 was seedling lethal. Sequence and transcriptional analysis showed that pTAC14 encodes a specific protein in plants that is located in the chloroplast associated with the thylakoid and that its expression depends on light. In addition, the transcript levels of all investigated PEP-dependent genes were clearly reduced in the ptac14-1 mutants, while the accumulation of nucleus-encoded phage-type RNA polymerase-dependent transcripts was increased, indicating an important role of pTAC14 in maintaining PEP activity. pTAC14 was found to interact with pTAC12/ HEMERA, another component of TACs that is involved in phytochrome signaling. The data suggest that pTAC14 is essential for proper chloroplast development, most likely by affecting PEP activity and regulating PEP-dependent plastid gene transcription in Arabidopsis together with pTAC12.

Rationale Chronic inflammation is a major contributor to the progressive pathology of hypertension and T cell activation is required for the genesis of hypertension. However, the precise role of myeloid cells in this process is unclear. Objective To characterize and understand the role of peripheral myeloid cells in the development of hypertension. Methods and Results We examined myeloid cells in the periphery of hypertensive mice and found that increased numbers of CD11b+Gr1+ myeloid cells in blood and the spleen is a characteristic of three murine models of experimental hypertension (Ang II, L-NAME, and high salt). These cells express surface markers and transcription factors associated with immaturity and immunosuppression. Also, they produce hydrogen peroxide to suppress T cell activation. These are characteristics of myeloid-derived suppressor cells (MDSCs). Depletion of hypertensive MDSCs increased blood pressure and renal inflammation. In contrast, adoptive transfer of wild-type MDSCs to hypertensive mice reduced blood pressure, while the transfer of NADPH oxidase 2-deficient MDSCs did not. Conclusions The accumulation of MDSCs is a characteristic of experimental models of hypertension. MDSCs limit inflammation and the increase of blood pressure through the production of hydrogen peroxide.

Transcriptionally active chromosome (TAC) is a fraction of protein/DNA complexes with RNA polymerase activity in the plastid. However, the function of most TAC proteins remains unknown. Here, we isolated two allelic mutants of the gene for a TAC component, TAC7, and performed functional analysis in plastid gene expression and chloroplast development in Arabidopsis. tac7-1 is a mutant with a premature translation termination isolated from a population treated with ethyl methane sulfonate, and tac7-2 is a transfer-DNA tagging mutant. Both of them showed an albino phenotype when grown under normal light conditions, and a few appressed membranes were observed inside the defective chloroplasts. These data indicate that TAC7 is important for thylakoid biogenesis. The TAC7 gene encodes an uncharacterized 161 amino acids polypeptide localized in chloroplast. The transcriptional levels of plastid-encoded polymerase (PEP)-dependent genes were downregulated in tac7-2, suggesting that PEP activity was decreased in the mutant. Yeast two-hybrid assay shows that TAC7 can interact with the four TAC components including FLN1, TAC10, TAC12 and TAC14 which are involved in redox state changes, phosphorylation processes and phytochrome-dependent light signaling, respectively, These data indicate that TAC7 plays an important role for TAC to regulate PEP-dependent chloroplast gene expression and chloroplast development.