An essential role of angiotensin II receptor type 1a in recipient kidney, not in transplanted peripheral blood leukocytes, in progressive immune-mediated renal injury

Citation
Y. Hisada et al., An essential role of angiotensin II receptor type 1a in recipient kidney, not in transplanted peripheral blood leukocytes, in progressive immune-mediated renal injury, LAB INV, 81(9), 2001, pp. 1243-1251
Citations number
37
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Medical Research General Topics
Journal title
LABORATORY INVESTIGATION
ISSN journal
0023-6837 → ACNP
Volume
81
Issue
9
Year of publication
2001
Pages
1243 - 1251
Database
ISI
SICI code
0023-6837(200109)81:9<1243:AEROAI>2.0.ZU;2-7
Abstract
Despite an intensive effort of elucidating the pathogenic role of angiotens in II (All) in immune-mediated renal injury, the precise mechanisms are poo rly understood. In the present study, we examined the site of All action, p eripheral blood leukocytes or resident renal cells, in immune-mediated rena l injury using All type 1a receptor (AT1a)-deficient homozygous (AT1a -/-) mice and wild-type (AT1a +/+) mice. The AT1a -/- mice showed delayed-type h ypersensitivity similar to that of the AT1a +/+ mice, suggesting that the l ack of AT1a does not impair a Th1-type cellular immune response of peripher al blood leukocytes involved in immune-mediated renal injury. We then gener ated the radiation bone marrow chimera mice, WA and AW, which have transpla nted peripheral blood leukocytes from the AT1a +/+ and AT1a -/- mice into t he AT1a -/- and AT1a +/+ mice, respectively. As controls, WW and AA, the AT 1a +/+ and AT1a -/- mice given bone marrow cells from the AT1a +/+ and AT1a -/- mice, respectively, were generated. Seven days after induction of anti glomerular basement membrane nephritis, glomerulosclerosis observed in the WW mice was markedly ameliorated in the WA mice, but not in the AW mice. In addition, the recruitment of monocytes/macrophages and the expressions of monocyte chemoattractant protein-1 and intercellular adhesion molecule-1 in the glomeruli of the AW and WW mice was evident, but such significant phen otypes were not seen in the WA and AA mice, showing a marked amelioration o f renal injury dependent on the host AT1a genotype. These results demonstra te an essential role of AT1a in intrinsic renal cells for progressive immun e-mediated renal injury and indicate a beneficial effect of blocking the re nin-angiotensin system in the treatment of such diseases.