Surfactant protein-A as an anti-inflammatory component in the amnion: implications for human pregnancy.
The mechanism of mouse parturition is thought to involve myometrial infiltration by amniotic fluid (AF) macrophages, activated by surfactant protein-A (SP-A). In humans, the concentration of AF SP-A decreases during labor, and no fetal macrophages are found in the myometrium after labor. Therefore, it appears that the mechanisms of labor in mice and humans are different. We investigated a potential role for SP-A in human pregnancy and parturition by examining SP-A expression patterns in AF and amnion. High molecular mass (>250 kDa) oligomeric SP-A was increased in AF with advancing gestation. Interestingly, these oligomers were more abundant in placental amnion before labor at term, while they increased primarily in reflected amnion during labor (p < 0.05). Immunoblotting showed a binding of high molecular mass SP-A in AF to amnion. In C57BL/6 mice, oligomeric SP-A was also readily detected in AF from E15 onwards, but not in amnion. Macrophage density in mice myometrium did not change with advancing gestational age. Microarray analysis of human amnion explants incubated with SP-A revealed a molecular signature of inhibited cytokine-cytokine receptor interaction with downregulation of IL-1beta, CXCL2, and CXCL5 mRNA expression. The findings in this study strongly suggest that SP-A signals amniotic anti-inflammatory response via AF during pregnancy. We propose that an SP-A interaction among AF, placental amnion, and reflected amnion is a unique mechanism for immunoregulation in human pregnancy akin to that established in lung biology. However, AF SP-A and fetal macrophages by themselves do not seem to be exclusive effectors of parturition in humans.
Lee
Deug-Chan
DC
Perinatology Research Branch, Department of Health and Human Services, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, USA.
Romero
Roberto
R
Kim
Chong Jai
CJ
Chaiworapongsa
Tinnakorn
T
Tarca
Adi L
AL
Lee
JoonHo
J
Suh
Yeon-Lim
YL
Mazaki-Tovi
Shali
S
Vaisbuch
Edi
E
Mittal
Pooja
P
Draghici
Sorin
S
Erez
Offer
O
Kusanovic
Juan Pedro
JP
Hassan
Sonia S
SS
Kim
Jung-Sun
JS
D000650:Amnion / Q000276:immunology*; D000653:Amniotic Fluid / Q000276:immunology*; D000818:Animals; D015153:Blotting, Western; D002469:Cell Separation; D002853:Chromatography, Liquid; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D047468:Immunoprecipitation; D018836:Inflammation Mediators / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D009215:Myometrium / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D036801:Parturition / Q000276:immunology*; D011247:Pregnancy / Q000276:immunology*; D037662:Pulmonary Surfactant-Associated Protein A / Q000032:analysis / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018836:Inflammation Mediators; D037662:Pulmonary Surfactant-Associated Protein A