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

CCR2 mediates the adverse effects of LPS in the pregnant mouse. Biol Reprod. 2019 Oct 10;: Authors: Hua R, Edey LF, O'Dea KP, Howe L, Herbert BR, Cheng W, Zheng X, MacIntyre DA, Bennett PR, Takata M, Johnson MR Abstract 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 hours in both groups of mice. At 7 hours 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 hours 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 was similar. Using the IP LPS model, we found that all measur...
Source: Reproductive Biology - Category: Reproduction Medicine Authors: Tags: Biol Reprod Source Type: research