PMID- 36417275
OWN - NLM
STAT- MEDLINE
DCOM- 20230116
LR  - 20240202
IS  - 1522-1466 (Electronic)
IS  - 1931-857X (Print)
IS  - 1522-1466 (Linking)
VI  - 324
IP  - 2
DP  - 2023 Feb 1
TI  - B2 cells contribute to hypertension and natural killer cell activation possibly 
      via AT1-AA in response to placental ischemia.
PG  - F179-F192
LID - 10.1152/ajprenal.00190.2022 [doi]
AB  - Preeclampsia, new onset hypertension during pregnancy, is associated with 
      activated T helper cells (Th) and B cells secreting agonistic autoantibodies 
      against the angiotensin II type 1 receptor (AT1-AA). The reduced uterine 
      perfusion pressure (RUPP) model of placental ischemia recapitulates these 
      characteristics. We have shown that Th-B cell communication contributes to AT1-AA 
      and symptoms of preeclampsia in the RUPP rat. B2 cells are classical B cells that 
      communicate with Th cells and are then transformed into memory B cells. We 
      hypothesize that B2 cells cause hypertension, natural killer (NK) cell 
      activation, and complement activation during pregnancy through the production of 
      AT1-AA. To test this hypothesis, total splenic B cells and B2 cells were isolated 
      from normal pregnant (NP) or RUPP rats on gestational day (GD)19 and adoptively 
      transferred into GD12 NP rats. A group of recipient rats was treated with a 
      specific inhibitor peptide of AT1-AA. On GD19, mean arterial pressure was 
      measured, tissues were collected, activated NK cells were measured by flow 
      cytometry, and AT1-AA was measured by cardiomyocyte assay. NP recipients of RUPP 
      B cells or RUPP B2 cells had increased mean arterial pressure, AT1-AA, and 
      circulating activated NK cells compared with recipients of NP B cells. 
      Hypertension in NP recipients of RUPP B cells or RUPP B2 was attenuated with 
      AT1-AA blockade. This study demonstrates that B cells and B2 cells from RUPP rats 
      cause hypertension and increased AT1-AA and NK cell activation in response to 
      placental ischemia during pregnancy.NEW & NOTEWORTHY This study demonstrates that 
      placental ischemia-stimulated B2 cells induce hypertension and circulating 
      natural killer cell activation and angiotensin II type 1 receptor production in 
      normal pregnant rats.
FAU - Herrock, Owen T
AU  - Herrock OT
AUID- ORCID: 0000-0002-9555-182X
AD  - Department of Pharmacology and Toxicology, University of Mississippi Medical 
      Center, Jackson, Mississippi.
FAU - Deer, Evangeline
AU  - Deer E
AUID- ORCID: 0000-0001-8004-5978
AD  - Department of Pharmacology and Toxicology, University of Mississippi Medical 
      Center, Jackson, Mississippi.
FAU - Amaral, Lorena M
AU  - Amaral LM
AUID- ORCID: 0000-0001-7581-9182
AD  - Department of Pharmacology and Toxicology, University of Mississippi Medical 
      Center, Jackson, Mississippi.
FAU - Campbell, Nathan
AU  - Campbell N
AD  - Department of Pharmacology and Toxicology, University of Mississippi Medical 
      Center, Jackson, Mississippi.
FAU - Lemon, James
AU  - Lemon J
AD  - Department of Pharmacology and Toxicology, University of Mississippi Medical 
      Center, Jackson, Mississippi.
FAU - Ingram, Nicole
AU  - Ingram N
AD  - Department of Pharmacology and Toxicology, University of Mississippi Medical 
      Center, Jackson, Mississippi.
FAU - Cornelius, Denise C
AU  - Cornelius DC
AUID- ORCID: 0000-0002-6730-6499
AD  - Emergency Medicine, University of Mississippi Medical Center, Jackson, 
      Mississippi.
FAU - Turner, Ty W
AU  - Turner TW
AD  - Department of Pharmacology and Toxicology, University of Mississippi Medical 
      Center, Jackson, Mississippi.
FAU - Fitzgerald, Sarah
AU  - Fitzgerald S
AD  - Department of Pharmacology and Toxicology, University of Mississippi Medical 
      Center, Jackson, Mississippi.
FAU - Ibrahim, Tarek
AU  - Ibrahim T
AD  - Department of Pharmacology and Toxicology, University of Mississippi Medical 
      Center, Jackson, Mississippi.
FAU - Dechend, Ralf
AU  - Dechend R
AD  - Experimental and Clinical Research Center, HELIOS Clinic, Max-Delbruck-Centrum 
      fur Molekulare Medizin, Berlin, Germany.
FAU - Wallukat, Gerd
AU  - Wallukat G
AD  - Experimental and Clinical Research Center, HELIOS Clinic, Max-Delbruck-Centrum 
      fur Molekulare Medizin, Berlin, Germany.
FAU - LaMarca, Babbette
AU  - LaMarca B
AUID- ORCID: 0000-0002-3340-6088
AD  - Department of Pharmacology and Toxicology, University of Mississippi Medical 
      Center, Jackson, Mississippi.
AD  - Department of Obstetrics and Gynecology, University of Mississippi Medical 
      Center, Jackson, Mississippi.
LA  - eng
GR  - P20 GM121334/GM/NIGMS NIH HHS/United States
GR  - R01 HD067541/HD/NICHD NIH HHS/United States
GR  - R01 HL151407/HL/NHLBI NIH HHS/United States
GR  - U54 GM115428/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20221123
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Autoantibodies)
RN  - 0 (Receptor, Angiotensin, Type 1)
SB  - IM
MH  - Humans
MH  - Rats
MH  - Pregnancy
MH  - Female
MH  - Animals
MH  - Placenta
MH  - *Pre-Eclampsia
MH  - Autoantibodies
MH  - Receptor, Angiotensin, Type 1/metabolism
MH  - Rats, Sprague-Dawley
MH  - *Hypertension
MH  - Killer Cells, Natural/metabolism
MH  - Ischemia/metabolism
MH  - Blood Pressure/physiology
PMC - PMC9844978
OTO - NOTNLM
OT  - B cells
OT  - autoantibodies
OT  - preeclampsia
COIS- No conflicts of interest, financial or otherwise, are declared by the authors.
EDAT- 2022/11/24 06:00
MHDA- 2023/01/17 06:00
PMCR- 2024/02/01
CRDT- 2022/11/23 12:32
PHST- 2022/11/24 06:00 [pubmed]
PHST- 2023/01/17 06:00 [medline]
PHST- 2022/11/23 12:32 [entrez]
PHST- 2024/02/01 00:00 [pmc-release]
AID - F-00190-2022 [pii]
AID - 10.1152/ajprenal.00190.2022 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2023 Feb 1;324(2):F179-F192. doi: 
      10.1152/ajprenal.00190.2022. Epub 2022 Nov 23.