(1104) The role of bone marrow-derived macrophage to prevent preterm birth in a murine model

The purpose of this study was to investigate the importance of macrophages in maintaining pregnancy and preventing preterm birth (PTB) in a murine model.

 


Study Design:

To induce PTB, Lipopolysaccharide (LPS) 25 ug in 100 ul PBS was injected in the middle of the first and second amniotic membranes in 16.5 dpc ICR mice. To deplete macrophages, clodronate liposomes were injected in 15.0, 15.5, and 16.0 dpc ICR mice intravenously. Macrophages in the bone marrow (BM), uterus, placenta, and decidua collected from 16.5dpc ICR mice were analyzed by fluorescence-activated single-cell sorting. Monocytes obtained from BM flushing were cultured to differentiate into macrophages (BMDMs), and then BMDMs were further polarized into M2-like macrophages using IL-4. M2-polarized BMDM was injected in 15.0 and 16.5 dpc mice treated with LPS to rescue LPS-induced PTB.  


Results:

The percentage of F4/80+ macrophages decreased 12 hours after the clodronate liposomes injection and PTB spontaneously occurred in 80% (4/5) of cases without LPS. F4/80+ macrophages were significantly reduced in bone marrow, uterus, placenta, and decidua of mice that received clodronate liposomes. Particularly, there was a significant decrease of F4/80+ macrophages in the BM. PTB occurred within 48 hours (4/4) in all mice in the LPS group, whereas the M2-polarized BMDM significantly reduced PTB in pregnant mice that received LPS. Only 25% of pregnant mice (1/4) with M2 BMDM therapy suffered from LPS-induced PTB.


Conclusion:

We demonstrate that balanced macrophage polarity could be a critical factor to maintain pregnancy and prevent inflammation-induced PTB in mice.