Adaptive and innate immune responses contribute to hypertension and hypertensive end-organ damage. Here, we determined the role of anaphylatoxin C5a, a major inflammatory effector of the innate immune system that is generated in response to complement activation, in hypertensive end-organ damage. For this purpose, we assessed the phenotype of C5a receptor 1 (C5aR1)-deficient mice in ANG II-induced renal and cardiac injury. Expression of C5aR1 on infiltrating and resident renal as well as cardiac cells was determined using a green fluorescent protein (GFP)-C5aR1 reporter knockin mouse. Flow cytometric analysis of leukocytes isolated from the kidney of GFP-C5aR1 reporter mice showed that 28% of CD45-positive cells expressed C5aR1. Dendritic cells were identified as the major C5aR1-expressing population (88.5%) followed by macrophages and neutrophils. Using confocal microscopy, we detected C5aR1 in the kidney mainly on infiltrating cells. In the heart, only infiltrating cells stained C5aR1 positive. To evaluate the role of C5aR1 deficiency in hypertensive injury, an aggravated model of hypertension was used. Unilateral nephrectomy was performed followed by infusion of ANG II (1.5 ng·g(-1)·min(-1)) and salt in wild-type (n = 34) and C5aR1-deficient mice (n = 32). C5aR1-deficient mice exhibited less renal injury, as evidenced by significantly reduced albuminuria. In contrast, cardiac injury was accelerated with significantly increased cardiac fibrosis and heart weight in C5aR1-deficient mice after ANG II infusion. No effect was found on blood pressure. In summary, the C5a:C5aR1 axis drives end-organ damage in the kidney but protects from the development of cardiac fibrosis and hypertrophy in experimental ANG II-induced hypertension.
The role of CXCR1, also known as fractalkine receptor, in hypertension is unknown. The present study determined the role of the fractalkine receptor CXCR1 in hypertensive renal and cardiac injury. Expression of CXCR1 was determined using CXCR1 mice that express a GFP reporter in CXCR1 cells. FACS analysis of leukocytes isolated from the kidney showed that 34% of CD45 cells expressed CXCR1. Dendritic cells were the majority of positive cells (67%) followed by macrophages (10%), NK cells (6%) and T cells (10%). Using confocal microscopy, the receptor was detected in the kidney only on infiltrating cells but not on resident renal cells. To evaluate the role of CXCR1 in hypertensive end-organ injury an aggravated model of hypertension was used. Unilateral nephrectomy was performed followed by infusion of Ang II (1.5 ng/g/min) and a high salt diet in wildtype (n=15) and CXCR1-deficient mice (n=18). CXCR1-deficiency reduced the number of renal dendritic cells and increased the numbers of renal CD11b/F4/80 macrophages and CD11b/Ly6G neutrophils in Ang II infused mice. Surprisingly, CXCR1-deficient mice exhibited increased albuminuria, glomerular injury and reduced podocyte density in spite of similar levels of arterial hypertension. In contrast, cardiac damage as assessed by increased heart weight, cardiac fibrosis and expression of fetal genes and matrix components was not different between both genotypes. Our findings suggest that CXCR1 exerts protective properties by modulating the invasion of inflammatory cells in hypertensive renal injury. CXCR1 inhibition should be avoided in hypertension because it may promote hypertensive renal injury.
Der Morbus Mondor bezeichnet ursprünglich eine oberflächliche Venenthrombose einer gesunden Vene entlang der anterolateralen thorakalen Brustwand. Mittlerweile werden auch oberflächliche Venenthrombosen anderer spezifischer Lokalisationen, beispielsweise am Penis, darunter subsumiert. Im folgenden Fallbericht stellen wir einen jungen Patienten mit einem nach einer beidseitigen inguinalen Crossektomie aufgetretenen penilen Morbus Mondor vor. Der Klinische FallWir berichten über einen sonst gesunden 48-jährigen Patienten, der sich 3 Wochen nach beidseitiger inguinaler Crossektomie in unserer Klinik vorstellte. Er berichtete von Schmerzen und einem Druckgefühl im Penis sowohl im unerigierten als auch im erigierten Zustand. Die Eigen-und die Familienanamnese in Bezug auf thromboembolische Erkrankungen wurden verneint. Das präoperative Blutbild sowie die Gerinnung zeigten keine Auffälligkeiten. Körperliche UntersuchungKlinisch zeigte sich eine tastbare Verhärtung ohne umgebende Rötung im Verlauf der Vena dorsalis penis superficialis und einer Vene am lateralen rechten Hoden (▶ Abb. 1 und ▶ Abb. 2).▶ Abb. 1 Klinischer Befund des penilen Morbus Mondor. ▶ Abb. 2 Klinischer Befund der V. dorsalis penis superficialis.
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