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| Item Type: | Article |
|---|---|
| Title: | Blockade of CD40 ligand for intercellular communication reduces hypertension, placental oxidative stress, and AT1-AA in response to adoptive transfer of CD4(+) T lymphocytes from RUPP rats |
| Creators Name: | Cornelius, D.C., Castillo, J., Porter, J., Amaral, L.M., Campbell, N., Paige, A., Thomas, A.J., Harmon, A., Cunningham, M.W., Wallace, K., Herse, F., Wallukat, G., Dechend, R. and LaMarca, B.D. |
| Abstract: | Preeclampsia (PE) is associated with altered immune activation during pregnancy. We have previously shown that adoptive transfer of CD4+ T cells from the reduced uterine perfusion pressure (RUPP) rat model of PE increases blood pressure, oxidative stress (ROS), and inflammation in normal pregnant recipient rats. The objective of this study was to determine if blockade of communication via the CD40-CD40 ligand (CD40L) interaction between placental ischemia-induced CD4+ T cells with endogenous normal pregnant (NP) cells would improve pathophysiology that was previously observed in NP recipient rats of RUPP CD4+ T cells. Splenic CD4+ T lymphocytes were magnetically separated, incubated with 2.5 {mu}g/ml anti-CD40 ligand ({alpha}CD40L) overnight, and transferred into NP rats on day 12 of gestation (NP+RUPP CD4+ T+anti-CD40L). On day 19 of gestation, blood pressure (MAP), blood, and tissues were collected. MAP was 99 +/- 2 in NP (n = 13), 116 +/- 4 in NP+RUPP CD4+ T cells (n = 7; P < 0.01); MAP only increased to 104 +/- 2 in NP+RUPP CD4+ T cells+CD40L (n = 24) (P < 0.05 vs. NP+RUPP CD4+ T cells). Mechanisms of hypertension in response to RUPP CD4+ T cells include endothelin-1 (ET-1), ROS, and angiotensin II type I receptor (AT1-AA) were analyzed. Inhibition of CD40L binding reduced placental ET-1 to 2.3-fold above NP rats and normalized placental ROS from 318.6 +/- 89 in NP+RUPP CD4+ T cells (P < 0.05) to 118.7 +/- 24 in NP+RUPP CD4+ T+anti-CD40L (P < 0.05). AT1-AA was also normalized with inhibition of CD40L. These data suggest that placental ischemia-induced T-cell communication via the CD40L is one important mechanism leading to much of the pathophysiology of PE. |
| Keywords: | Hypertension, Preeclampsia, T-cells, Animals, Rats |
| Source: | American Journal of Physiology Regulatory Integrative and Comparative Physiology |
| ISSN: | 0363-6119 |
| Publisher: | American Physiological Society |
| Volume: | 309 |
| Number: | 10 |
| Page Range: | R1243-R1250 |
| Date: | 15 November 2015 |
| Official Publication: | https://doi.org/10.1152/ajpregu.00273.2015 |
| PubMed: | View item in PubMed |
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