Possible Roles of Proinflammatory and Chemoattractive Cytokines Produced by Human Fetal Membrane Cells in the Pathology of Adverse Pregnancy Outcomes Associated with Influenza Virus Infection

Figure 6

Multistage roles of chemoattractive cytokines and MDI factor produced by chorion, amnion mesenchymal, and amnion epithelial cells in the recruitment and differentiation of phagocytes. When influenza viruses spread from mother to the chorion cell layer at the first stratum, ENA-78, GRO-α/β, and IL-8 may be firstly produced to recruit a first unit of neutrophils by only chorion cells that are located on the maternal-fetal interface. The chorion cells may produce MCP-1, IP-10, RANTES, and MIP-1β to recruit maternal circulating monocyte, IL-6, TNF-α, and IFN-β to differentiate the recruited maternal monocytes, and the staying fetal amnion mesenchymal cells to macrophages. When the viruses got over the chorion cell layer and spread to the amnion mesenchymal cell layer at the second stratum, the amnion mesenchymal cells may produce GRO-α/β and IL-8 to recruit a second unit of neutrophils as reinforcements, MCP-1, IP-10, RANTES, and MIP-1β to recruit maternal circulating monocytes, and IL-6, TNF-α and IFN-β to differentiate the recruited maternal monocytes and the staying fetal amnion mesenchymal cells to macrophages as well as the chorion cells. If the virus spread to the amnion epithelium as a final cellular barrier, the amnion epithelial cells may produce IL-8 to recruit a third unit of neutrophils and RANTES and MIP-1β to recruit fetus-derived macrophages differentiated from the staying amnion mesenchymal cells. Abbreviations used: ENA-78, epithelial cell-derived neutrophil-activating protein 78; GRO-α/β, growth-related oncogene α/β; IL, interleukin; IP-10, interferon inducible protein 10; MCP-1, monocyte chemoattractant protein 1; MDI, monocyte differentiation-inducing; MIP-1β, macrophage inflammatory protein 1β; RANTES, regulated on activation, normal T cell expressed and secreted.