Association Between Angiopoietin-2 and Enterovirus 71 Induced Pulmonary Edema

Qi, Zhijiang; Li, Zhi; Hao, Dong; Wang, Tao; Xia, Yongfu; Sun, Ting; Wang, Juan; Zhuang, Fuju; Wang, Xiaozhi

OBJECTIVE: To characterize pulmonary edema (PE) fluid induced by enterovirus 71 (EV71) infection, elucidate the relationship between angiopoietin-2 (Ang-2) and PE, and explore the pathogenesis of PE. METHODS: Clinical data were collected from critical infants with EV71 infection. The infants were grouped into PE, non-PE, and control groups. The control group included infants in the preoperative period of elective inguinal hernia surgery. Biochemical changes in PE fluid were evaluated, and Ang-2 levels in serum and PE fluid were measured. Human pulmonary microvascular endothelial cells (HPMECs) were incubated with serum from the control and PE groups and human recombinant Ang-2 or serum from the PE group and human recombinant Ang-1, and changes in the intercellular junctions were recorded via immunofluorescence. RESULTS: Of the 161 infants with critical EV71 infection admitted to the hospital, 39 had PE. PE fluid was collected from 18 of these infants. The PE fluid-to-serum (P/S) ratio of total protein was 0.9 ± 0.2, and all P/S ratios of albumin were 1.0 ± 0.3. The Ang-2 level was higher in the non-PE group (333.2 ± 79.7 pg/ml) than in the control group (199.9 ± 26.7 pg/ml), although without statistical significance (P = 0.115). The Ang-2 level in the PE group (2819.2 ± 908.7 pg/ml) was higher than those in both the non-PE and the control groups (both, P < 0.001). Serum samples from the PE group had damaged cell junctions of confluent HPMEC monolayers that were reversed by Ang-1. CONCLUSIONS: The PE fluid of infants with EV71-induced PE was protein-rich, and elevated Ang-2 expression was associated with PE. The mechanism through which PE develops may be related to Ang-2-induced cell junction damage.