削弱LPA1功能抑制傷口癒合過程中嗜中性球之聚集

Abstract

We have previously demonstrated the necessity of a lysophosphatidic acid (LPA) receptor, LPA1, in zebrafish lymphangiogenesis. One of the major functions of lymphatic system is to exert inflammatory response. Therefore, we examined the possible role of LPA1 in zebrafish imflammation. Here we performed a live-imaging analysis of neutrophil recruitment by using a transgenic zebrafish (Tg(MPO:EGFP)114), which expressed EGFP in neutrophils. The lpa1 morpholino (MO) caused a dose-dependent reduction in neutrophil recruitment to the wound site and this defect could be rescued completely by overexpression of lpa1. Flow cytometry analysis reveals that no significant change in the total number of neutrophil in the lpa1 morphants. Furthermore, the expressions of myelopoiesis-related genes, including mpx, lcp1 and spi1 were not affected by the lpa1 knockdown, either. These results demonstrated that the lpa1 MO exerted specific inhibition on neutrophilic inflammation. In addition, we provided evidence that knockdown of LPA1 has no significant effect on tail fin regeneration. Thus, we conclude that LPA1 specifically mediates neutrophilic inflammatory response in zebrafish.