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 7

Hypothetical tissue injury model with special emphases of the interaction between human fetal membrane chorion cells and two types of phagocytes. Influenza virus infection induces apoptosis and the gene expression of the MDI factor (i.e., IL-6, TNF-α and IFN-β), monocyte-attractive chemokines (MCP-1, RANTES, MIP-1β and IP-10) and neutrophil-attractive chemokines (IL-8, GRO-α/β and ENA-78) in human fetal membrane chorion cells. The monocyte- and neutrophil-attractive chemokines recruit maternal monocytes and neutrophils circulating in the bloodstream into the infected region, respectively. The MDI factor (i.e., IL-6, TNF-α and IFN-β) differentiates the recruited maternal monocytes and the staying fetal amnion mesenchymal cells to mature macrophages. The mature macrophages and neutrophils phagocytose the apoptotic cell debris of chorion cells resulting from apoptosis. Subsequent to phagocytosis, an abrupt increase in superoxide production by macrophages and neutrophils, known as the oxidative burst, occurs, which is catalyzed by NADPH oxidase enzyme complex. Superoxide produced by phagocytes engulfing chorion cells undergoing apoptosis may injure tissues through inducing apoptosis in noninfected cells in vivo situation, resulting in the formation of necrotic foci. 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; NADPH, nicotinamide adenine dinucleotide phosphate; RANTES, regulated on activation, normal T cell expressed and secreted.