CCR2 mediates the adverse effects of LPS in the pregnant mouse
| Autor: | Laura G. Howe, David A. MacIntyre, Xia Zheng, Lydia F Edey, Mark R. Johnson, Kieran P. O'Dea, Weiwei Cheng, Renyi Hua, Bronwen R. Herbert, Masao Takata, Philip R. Bennett |
|---|---|
| Přispěvatelé: | Chelsea & Westminster Health Charity, CW+ |
| Rok vydání: | 2019 |
| Předmět: |
Lipopolysaccharides
0301 basic medicine Chemokine Receptors CCR2 Placenta animal diseases chemokines Inflammation CCL2 Monocytes Proinflammatory cytokine Sepsis Andrology 03 medical and health sciences leucocytes Obstetric Labor Premature 0302 clinical medicine Pregnancy parasitic diseases medicine Animals Arterial Pressure Obstetrics & Reproductive Medicine lungs 11 Medical and Health Sciences Mice Knockout biology Macrophages Parturition Myometrium hemic and immune systems Cell Biology General Medicine 06 Biological Sciences medicine.disease Disease Models Animal 030104 developmental biology medicine.anatomical_structure Reproductive Medicine 030220 oncology & carcinogenesis biology.protein CCR2 Female medicine.symptom |
| Zdroj: | Biology of Reproduction. 102:445-455 |
| ISSN: | 1529-7268 0006-3363 |
| Popis: | 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.Summary SentenceThis study used mouse models of preterm labour and sepsis to show that during pregnancy the CCL2/CCR2 system is important in the cardiovascular response to sepsis but while it delays pup death it does not delay LPS-induced preterm labour. |
| Databáze: | OpenAIRE |
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