The hormone renin plays a crucial role in the regulation of blood pressure and fluidelectrolyte homeostasis. Normally, renin is synthesized by juxtaglomerular (JG) cells, a specialized group of myoepithelial cells located near the entrance to the kidney glomeruli. In response to low blood pressure and/or a decrease in extracellular fluid volume (as it occurs during dehydration, hypotension, or septic shock) JG cells respond by releasing renin to the circulation to reestablish homeostasis. Interestingly, renin-expressing cells also exist outside of the kidney, where their function has remained a mystery. We discovered a unique type of renin-expressing B-1 lymphocytes that may have unrecognized roles in defending the organism against infections.These cells synthesize and release renin, entrap and phagocyte bacteria and control bacterial growth. The ability of renin-bearing lymphocytes to control infections -which is enhanced by the presence of renin -adds a novel, previously unsuspected dimension to the defense role of reninexpressing cells, linking the endocrine control of circulatory homeostasis with the immune control of infections to ensure survival. the generation of angiotensin(s), vasoconstriction, sodium chloride reabsorption and reestablishment of fluid electrolyte and blood pressure balance(21). Similarly, peritoneal B-1 renin cells which have the capability to recognize, entrap, phagocyte and kill bacteria, act as an early line of defense to counteract and stop the threat. Interestingly, the presence of renin renders B-1 lymphocytes more effective in bacterial killing, suggesting that renin per se may have an added role in the degradation of bacterial components.Thus, renin, and the diverse group of cells that synthesize it, are at the epicenter of two systems crucial for survival: the endocrine renin-angiotensin system driven to maintain cardiocirculatory homeostasis by regulating volume and tissue perfusion and the innate immune system designed for the rapid control of infections.
METHODS (Complete Methods included in Supplemental Data)Mice: Ren1 dCre/+ mice express Cre recombinase in renin cells(6). Ren1 dcre/+ mice were bred to the lineage reporter line mT/mG, in which non-recombined cells express mTd and Cre-mediated recombined cells express GFP(22). Thus, GFP is expressed in renin-expressing cells and all descendants. Ren1 c-YFP transgenic mice express YFP in cells that actively express renin and were used to identify cells that actively express renin(17). Ren1 c-/-Ren1 c-YFP mice are renin knockout mice which also express YFP in cells that attempt to express renin.
Cells:Peritoneal cells were obtained from WT (Ren1 c-YFP ) and renin knockout (Ren1 c-/-Ren1 c-YFP ) mice. Briefly, mice were anesthetized, and scissors and forceps were used to remove the skin overlying the ventral portion of the peritoneum. 5 mL of PBS with 3% FBS was injected into the peritoneal cavity with a 30 gauge needle. The peritoneum was then massaged for 5 minutes to mobilize cells into the PBS solution. An 18 gauge needle wa...