Ham Hwa-Yong, Kang Shin-Hae, Song Dong-Keun
Department of Pharmacology, Hallym University College of Medicine, Chuncheon 24252, Korea.
Korean J Physiol Pharmacol. 2022 May 1;26(3):175-182. doi: 10.4196/kjpp.2022.26.3.175.
Translocation of azurophil granules is pivotal for bactericidal activity of neutrophils, the first-line defense cells against pathogens. Previously, we reported that lysophosphatidylcholine (LPC), an endogenous lipid, enhances bactericidal activity of human neutrophils increasing translocation of azurophil granules. However, the precise mechanism of LPC-induced azurophil granule translocation was not fully understood. Treatment of neutrophil with LPC significantly increased CD63 (an azurophil granule marker) surface expression. Interestingly, cytochalasin B, an inhibitor of action polymerization, blocked LPC-induced CD63 surface expression. LPC increased F-actin polymerization. LPC-induced CD63 surface expression was inhibited by both a Rho specific inhibitor, Tat-C3 exoenzyme, and a Rho kinase (ROCK) inhibitor, Y27632 which also inhibited LPC-induced F-actin polymerization. LPC induced Rho-GTP activation. NSC23766, a Rac inhibitor, however, did not affect LPC-induced CD63 surface expression. Theses results suggest a novel regulatory mechanism for azurophil granule translocation where LPC induces translocation of azurophil granules Rho/ROCK/F-actin polymerization pathway.
嗜天青颗粒的易位对于中性粒细胞（抵御病原体的一线防御细胞）的杀菌活性至关重要。此前，我们报道过溶血磷脂酰胆碱（LPC），一种内源性脂质，可通过增加嗜天青颗粒的易位来增强人类中性粒细胞的杀菌活性。然而，LPC诱导嗜天青颗粒易位的确切机制尚未完全明确。用LPC处理中性粒细胞可显著增加CD63（一种嗜天青颗粒标志物）的表面表达。有趣的是，细胞松弛素B，一种肌动蛋白聚合作用的抑制剂，可阻断LPC诱导的CD63表面表达。LPC增加F-肌动蛋白聚合。LPC诱导的CD63表面表达受到Rho特异性抑制剂Tat-C3外切酶和Rho激酶（ROCK）抑制剂Y27632的抑制，这两种抑制剂也抑制LPC诱导的F-肌动蛋白聚合。LPC诱导Rho-GTP活化。然而，Rac抑制剂NSC23766并不影响LPC诱导的CD63表面表达。这些结果提示了一种嗜天青颗粒易位的新型调节机制，即LPC通过Rho/ROCK/F-肌动蛋白聚合途径诱导嗜天青颗粒易位。
