Lambermont Verena A, Kuypers Elke, Collins Jennifer J P, Pillow J Jane, Newnham John P, Polglase Graeme R, Nitsos Ilias, Kemp Matthew W, Jobe Alan H, Kallapur Suhas G, Kramer Boris W
Department of Pediatrics, Maastricht University Medical Center, Maastricht, The Netherlands.
School of Women's and Infants Health, University of Western Australia, Perth, Australia.
Pediatr Res. 2014 Apr;75(4):500-6. doi: 10.1038/pr.2014.3. Epub 2014 Jan 17.
Intra-amniotic lipopolysaccharide (LPS) exposure may affect neonatal outcome by altering fetal lung and immune system development. We hypothesized that intra-amniotic LPS exposure would cause persistent fetal pulmonary responses as the lungs develop in utero.
Fetal lambs were exposed to intra-amniotic LPS at 118 or at 118 and 123 d of gestational age (GA) with delivery at 125, 133, or 140 d (term = 147 d). Immune responses, PU.1 expression, Toll-like receptor (TLR)-1,2,4,6 mRNA levels, mast cell levels, and pulmonary elastin deposition were evaluated.
After a single dose of LPS, pulmonary inflammatory responses were observed with increases of (i) PU.1 and TLR1 at 125 d GA and (ii) monocytes, lymphocytes, TLR2, and TLR6 at 133 d GA. Repetitive LPS exposure resulted in (i) increases of neutrophils, monocytes, PU.1, and TLR1 at 125 d GA; (ii) increases of neutrophils, PU.1, and TLR2 at 133 d GA; and (iii) decreases of mast cells, elastin foci, TLR4, and TLR6 at early gestation. At 140 d GA, only PU.1 was increased after repetitive LPS exposure.
The preterm fetal lung can respond to a single exposure or repeated exposures from intra-amniotic LPS in multiple ways, but the absence of inflammatory and structural changes in LPS-exposed fetuses delivered near term suggest that the fetus can resolve an inflammatory stimulus in utero with time.
羊膜腔内暴露于脂多糖（LPS）可能通过改变胎儿肺和免疫系统发育来影响新生儿结局。我们假设羊膜腔内暴露于LPS会在胎儿肺在子宫内发育时引起持续的胎儿肺部反应。
将胎羊在妊娠118天或妊娠118天和123天时羊膜腔内暴露于LPS，分别于125天、133天或140天（足月为147天）分娩。评估免疫反应、PU.1表达、Toll样受体（TLR）-1、2、4、6 mRNA水平、肥大细胞水平和肺弹性蛋白沉积。
单次注射LPS后，在妊娠125天时观察到肺部炎症反应，表现为（i）PU.1和TLR1增加，以及在妊娠133天时（ii）单核细胞、淋巴细胞、TLR2和TLR6增加。重复暴露于LPS导致（i）在妊娠125天时中性粒细胞、单核细胞、PU.1和TLR1增加；（ii）在妊娠133天时中性粒细胞、PU.1和TLR2增加；以及（iii）在妊娠早期肥大细胞、弹性蛋白灶、TLR4和TLR6减少。在妊娠140天时，重复暴露于LPS后仅PU.1增加。
早产胎儿肺可对羊膜腔内LPS的单次暴露或重复暴露产生多种反应，但足月分娩的LPS暴露胎儿无炎症和结构变化表明胎儿可随时间在子宫内解决炎症刺激。
