| First Author | Hua R | Year | 2020 |
| Journal | Biol Reprod | Volume | 102 |
| Issue | 2 | Pages | 445-455 |
| PubMed ID | 31599921 | Mgi Jnum | J:288880 |
| Mgi Id | MGI:6416396 | Doi | 10.1093/biolre/ioz188 |
| Citation | Hua R, et al. (2020) CCR2 mediates the adverse effects of LPS in the pregnant mouse. Biol Reprod 102(2):445-455 |
| abstractText | In our earlier work, we found that intrauterine (i.u.) and intraperitoneal (i.p.) injection of LPS (10-mug 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. |
