CCR2 mediates the adverse effects of LPS in the pregnant mouse.

Renyi Hua, Lydia F Edey, Kieran P O'Dea, Laura Howe, Bronwen R Herbert, Weiwei Cheng, Xia Zheng, David A MacIntyre, Philip R Bennett, Masao Takata, Mark R Johnson

Biology of reproduction 2020 Feb 14

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In our earlier work, we found that intrauterine (i.u.) and intraperitoneal (i.p.) injection of LPS (10-μg serotype 0111:B4) induced preterm labor (PTL) with high pup mortality, marked systemic inflammatory response and hypotension. Here, we used both i.u. and i.p. LPS models in pregnant wild-type (wt) and CCR2 knockout (CCR2-/-) mice on E16 to investigate the role played by the CCL2/CCR2 system in the response to LPS. Basally, lower numbers of monocytes and macrophages and higher numbers of neutrophils were found in the myometrium, placenta, and blood of CCR2-/- vs. wt mice. After i.u. LPS, parturition occurred at 14 h in both groups of mice. At 7 h post-injection, 70% of wt pups were dead vs. 10% of CCR2-/- pups, but at delivery 100% of wt and 90% of CCR2-/- pups were dead. Myometrial and placental monocytes and macrophages were generally lower in CCR2-/- mice, but this was less consistent in the circulation, lung, and liver. At 7 h post-LPS, myometrial ERK activation was greater and JNK and p65 lower and the mRNA levels of chemokines were higher and of inflammatory cytokines lower in CCR2-/- vs. wt mice. Pup brain and placental inflammation were similar. Using the IP LPS model, we found that all measures of arterial pressure increased in CCR2-/- but declined in wt mice. These data suggest that the CCL2/CCR2 system plays a critical role in the cardiovascular response to LPS and contributes to pup death but does not influence the onset of inflammation-induced PTL. © The Author(s) 2019. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Citation

Renyi Hua, Lydia F Edey, Kieran P O'Dea, Laura Howe, Bronwen R Herbert, Weiwei Cheng, Xia Zheng, David A MacIntyre, Philip R Bennett, Masao Takata, Mark R Johnson. CCR2 mediates the adverse effects of LPS in the pregnant mouse. Biology of reproduction. 2020 Feb 14;102(2):445-455