PMID- 37615049
OWN - NLM
STAT- MEDLINE
DCOM- 20230928
LR  - 20240222
IS  - 1522-1466 (Electronic)
IS  - 1931-857X (Print)
IS  - 1522-1466 (Linking)
VI  - 325
IP  - 5
DP  - 2023 Nov 1
TI  - Macrophage angiotensin AT(2) receptor activation is protective against early 
      phases of LPS-induced acute kidney injury.
PG  - F552-F563
LID - 10.1152/ajprenal.00177.2022 [doi]
AB  - Lipopolysaccharide (LPS)-induced acute kidney injury (AKI) is characterized by 
      inflammation and infiltration of immune cells, mainly neutrophils and 
      macrophages, and results in sudden renal dysfunction. Previously, we have 
      reported the anti-inflammatory and renoprotective role of the angiotensin II type 
      2 receptor (AT(2)R), expressed on kidney tubular cells and immune cells, in 
      LPS-induced AKI. Moreover, in vitro studies revealed macrophage AT(2)R activation 
      shifts the cells to the anti-inflammatory M2 subtype. However, the protective 
      role of the macrophage AT(2)R in a model of AKI is unknown. The present study 
      addressed this question by adoptive transfer of bone marrow-derived macrophages 
      (BMDMs) in systemic macrophage-depleted mice. We acquired significant systemic 
      macrophage depletion by two doses of liposomal clodronate (CLD), and the mice 
      were repopulated with BMDMs (CD11b(+)F4/80(+), double positive) primed with 
      AT(2)R agonist C21 (CLD + MacC21 + LPS) or vehicle (CLD + Mac + LPS) in vitro for 
      60 min, followed by LPS (5 mg/kg body wt ip) challenge. We observed a gradual 
      increase in the CD11b(+) cells at 2 and 24 h after the LPS challenge. However, 
      kidney CD11b(+) cells in the CLD + Mac + LPS group were elevated compared with 
      the CLD + MacC21 + LPS group at 2 h after the LPS challenge. The level of 
      inflammatory cytokine (tumor necrosis factor-alpha) was elevated at 2 h, which was 
      reduced significantly in CLD + MacC21 + LPS-treated animals. Also, CLD + MacC21 + 
      LPS-treated animals had elevated plasma and renal IL-10, indicating an 
      anti-inflammatory role of C21-treated BMDMs. Renal functional injury in CLD + 
      MacC21 + LPS-treated animals was partially improved. Collectively, the data 
      demonstrate that BMDM AT(2)R stimulation results in anti-inflammation and partial 
      renoprotection against early stages of LPS-induced AKI.NEW & NOTEWORTHY Endotoxin 
      such as lipopolysaccharide (LPS) induces acute kidney injury (AKI), which is a 
      risk factor for and often leads to chronic kidney diseases. The present study 
      revealed that bone marrow-derived macrophage activation of the angiotensin II 
      type 2 receptor (AT(2)R) contributes to the anti-inflammation and partial 
      renoprotection against early stages of LPS-induced AKI. Since AT(2)R is an 
      emerging anti-inflammatory and organ-protective target, this study advances our 
      understanding of AT(2)R's anti-inflammatory mechanisms associated with 
      renoprotection.
FAU - Fatima, Naureen
AU  - Fatima N
AUID- ORCID: 0000-0002-7839-8827
AD  - Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, 
      University of Houston, Houston, Texas, United States.
FAU - Ali, Riyasat
AU  - Ali R
AD  - Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, 
      University of Houston, Houston, Texas, United States.
FAU - Faisal, Tahmid
AU  - Faisal T
AUID- ORCID: 0000-0002-5523-407X
AD  - Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, 
      University of Houston, Houston, Texas, United States.
FAU - Kulkarni, Kalyani
AU  - Kulkarni K
AD  - Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, 
      University of Houston, Houston, Texas, United States.
FAU - Patel, Sanket
AU  - Patel S
AUID- ORCID: 0000-0003-1674-711X
AD  - Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, 
      University of Houston, Houston, Texas, United States.
FAU - Hussain, Tahir
AU  - Hussain T
AUID- ORCID: 0000-0002-6353-2317
AD  - Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, 
      University of Houston, Houston, Texas, United States.
LA  - eng
GR  - R01 DK061578/DK/NIDDK NIH HHS/United States
GR  - R01 DK117495/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20230824
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Receptor, Angiotensin, Type 2)
RN  - RC2V4W0EYC (compound 21)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Angiotensins)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Lipopolysaccharides/toxicity
MH  - Receptor, Angiotensin, Type 2
MH  - *Acute Kidney Injury/chemically induced/prevention & control
MH  - Macrophages/pathology
MH  - Anti-Inflammatory Agents/pharmacology
MH  - Angiotensins
MH  - Mice, Inbred C57BL
PMC - PMC10878726
OTO - NOTNLM
OT  - acute kidney injury
OT  - angiotensin II type 2 receptor
OT  - compound 21
OT  - lipopolysaccharide
OT  - macrophage
COIS- No conflicts of interest, financial or otherwise, are declared by the authors.
EDAT- 2023/08/24 06:42
MHDA- 2023/09/28 06:42
PMCR- 2024/11/01
CRDT- 2023/08/24 04:14
PHST- 2024/11/01 00:00 [pmc-release]
PHST- 2023/09/28 06:42 [medline]
PHST- 2023/08/24 06:42 [pubmed]
PHST- 2023/08/24 04:14 [entrez]
AID - F-00177-2022 [pii]
AID - 10.1152/ajprenal.00177.2022 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2023 Nov 1;325(5):F552-F563. doi: 
      10.1152/ajprenal.00177.2022. Epub 2023 Aug 24.