Effects of Co-culture of AGM-S3 Stromal Cells on Spontaneous Apoptosis and Immune Function of Neutrophils
Wang Yongrong, Fan Yulong, Lü Mengnan, Ma Runzhi, Sun Mengyu, Kong Xinyao, Wang Tong, Feng Sizhou, Han Mingzhe, Xu Yuanfu*
AGM-S3, a cell line derived from the aorta-gonad-mesonephros (AGM) region. We established a co-culture system in vitro to study the effect of AGM-S3 cells on the neutrophils. The results showed that co-culture with AGM-S3 cells could significantly delayed neutrophils death (the half-life was extended from 20 h to 48 h), maintained the functions of chemotaxis, phagocytosis and the release of reactive oxygen species (ROS) as well. Further studies indicated that AGM-S3 cells mainly activated pro-survival signaling pathways (such as Akt) in neutrophils by secreting cytokines (such as IL-6, MCP-1, and IL-1α, etc.), which promoted the continuous expression of Mcl-1/Bcl-xl and inhibited the activation of Caspase-3. In the mouse model of peritonitis, neutrophils co-cultured for 24 h were reinfused from the tail vein into mice, and they could be recruited to the abdominal inflamation site. Our results indicated that AGM-S3 cells were durable in maintaining the survival and function of neutrophils in vitro, furthermore, those neutrophils bear normal immunological activity after being refused to mice. This study will provide new strategies and experimental basis for future studies on infusion of granulocytes in patients with granulocyte deficiency or refractory infection, as well as functional modification of neutrophils.
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