Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
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Advances in Clinical and Experimental Medicine

2009, vol. 18, nr 6, November-December, p. 623–639

Publication type: review article

Language: English

Immune Processes at the Level of the Juxtaglomerular Apparatus and Their Relationship with Hypertension and Immune−Mediated Nephropathies – State of the Art

Procesy immunologiczne w obrębie aparatu przykłębuszkowego i ich związek z nadciśnieniem tętniczym i chorobami nerek o podłożu immunologicznym

Gheorghe Gluhovschi1,, Cristina Gluhovschi1,, Flaviu Bob1,, Silvia Velciov1,, Virginia Trandafirescu1,, Ligia Petrica1,, Gheorghe Bozdog1,, Daniel Cioca2,

1 Nephrology Department, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania

2 Center for Immunophysiology and Biotechnologies, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania, and the Austrian Academy of Sciences, Immunology Division, Innsbruck, Austria

Abstract

The paper presents aspects of immune processes at the level of the juxtaglomerular apparatus (JGA) and their relationship with hypertensive pathology and immune−mediated glomerular nephropathies. In various immune−mediated diseases of the JGA, such as, among others, systemic lupus erythematosus (SLE), IgA nephropathy, and diabetes mellitus, markers of immune processes are present. During immune processes that affect the extraglomerular mesangium by means of immune deposits or immune cells, the transmission of information from the level of the macula densa to the afferent arteriole can be perturbed, with alteration of the tubulo−glomerular feedback and with probable perturbation of the mechanisms of blood pressure regulation. Blood vessels, predominantly the afferent arteriole, participate in immune processes such as vasculitis, acute antibody−mediated graft rejection, and nephrosclerosis, which are all associated with hypertension. The occurrence of JGA vessel lesions during immunemediated diseases which themselves affect the JGA could amplify the severity of hypertension in these diseases. Because in some diseases, such as diabetes mellitus, diminution of the lumen of JGA vessels has been found, the suspicion arises that lesions of the respective afferent arterioles may cause Goldblatt−like phenomena, and because the lesion is diffuse, we are faced with a sum of Goldblatt phenomena, which may cause a lesion similar to that encountered in renal artery stenosis. The extraglomerular mesangium of the JGA communicates with the intraglomerular mesangium. Some studies plead for the fact that the cells of the extraglomerular mesangium are involved in regenerative processes of the intraglomerular mesangium, which is damaged in glomerulonephritis. CD34 markers encountered at the level of stem cells have been evidenced at the level of the extraglomerular mesangium. Intrarenal RAS could play an important role in the arterial hypertension pathogenesis of AHT (arterial hypertension) and in glomerular nephropathy. It can be an alternative to or a completion of the role of the JGA.

Streszczenie

Praca opisuje procesy immunologiczne w obrębie aparatu przykłębuszkowego (JGA) i ich związki z nadciśnieniem tętniczym i kłębuszkowymi chorobami nerek o podłożu immunologicznym. W wielu chorobach o podłożu immunologicznym, takich jak: toczeń rumieniowaty układowy (SLE), nefropatia IgA i cukrzyca, występują markery procesów immunologicznych. Podczas procesów immunologicznych, które wpływają na mezangium zewnętrzne za pomocą depozytu immunologicznego lub komórek odpornościowych, przekazywanie informacji z plamki gęstej do doprowadzających tętniczek może być zaburzony, a także mogą wystąpić zmiany sprzężenia cewkowo−kłębuszkowego oraz możliwe zaburzenia mechanizmu regulacji ciśnienia krwi. Naczynia krwionośne, głównie doprowadzające tętniczki, uczestniczą w procesach immunologicznych, takich jak: zapalenia naczyń, ostre odrzucenie przeszczepu mediowane przez przeciwciała, miażdżycopochodne stwardnienie nerki, z których wszystkie są związane z nadciśnieniem. Występowanie uszkodzeń naczyń w JGAw czasie chorób o podłożu odpornościowym, które same mogą naruszać JGA, mogłoby zwiększyć nasilenie nadciśnienia w tych chorobach. Ponieważ w niektórych chorobach, takich jak cukrzyca, wykryto zmniejszenie światła naczyń JGA, podejrzewa się, że zmiany w odpowiednich doprowadzających tętniczkach mogą wywołać zmiany podobne do zjawiska Goldblatta, a ponieważ zmiany są rozlane, występuje suma zjawisk Goldblatta, które mogą wywoływać uszkodzenia podobne do spotykanych w zwężeniu tętnicy nerkowej. Mezangium zewnętrzne JGA komunikuje się z mezangium wewnętrznym. Niektóre badania powołują się na to, że komórki mezangium zewnętrznego są zaangażowane w procesy regeneracyjne mezangium wewnętrznego, które jest uszkodzone w kłębuszkowym zapaleniu nerek. Markery CD34 występujące w komórkach macierzystych zostały wykryte także w mezangium zewnętrznym. Zwężenie tętnicy nerkowej może odgrywać istotną rolę w patogenezie nadciśnienia tętniczego i kłębuszkowego zapalenia nerek. Może być alternatywą lub uzupełnieniem roli JGA.

Key words

JGA, immunopathology, vascular disease, glomerulopathy

Słowa kluczowe

JGA, immunopatologia, choroba naczyń, uszkodzenie kłębuszków nerkowych

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