PROPIONATE INDUCES POLYMORPHONUCLEAR LEUKOCYTE ACTIVATION AND INHIBITS FORMYLMETHIONYL-LEUCYL-PHENYLALANINE-STIMULATED ACTIVATION
PROPIONATE INDUCES POLYMORPHONUCLEAR LEUKOCYTE ACTIVATION AND INHIBITS FORMYLMETHIONYL-LEUCYL-PHENYLALANINE-STIMULATED ACTIVATION
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DOI：
10.1128/iai.60.7.2957-2968.1992
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发表时间：
1992-07-01
影响因子：
3.1
通讯作者：
NIEDERMAN, R
中科院分区：
文献类型：
--
作者：
BRUNKHORST, BA;KRAUS, E;NIEDERMAN, R
短链羧酸（SCCA）是病原菌代谢的副产物，可改变细胞质pH值，抑制多种多形核白细胞（PMN）运动功能。由于细胞骨架F-肌动蛋白的改变是中央PMN的流动性，在这项研究中，我们研究了SCCA对细胞骨架F-肌动蛋白的影响。最初，我们测试了9种SCCA（甲酸盐、乙酸盐、丙酸盐、丁酸盐、戊酸盐、己酸盐、乳酸盐、琥珀酸盐和异丁酸盐）。我们在这里的文件，而8改变细胞质pH值，只有6改变细胞骨架F-肌动蛋白。然后，我们选择了一个SCCA，改变F-肌动蛋白和细胞质的pH值（丙酸）和一个SCCA，改变细胞质的pH值（乳酸）进行进一步的研究。丙酸，而不是乳酸，导致不规则的细胞形状和F-肌动蛋白分布。此外，丙酸，但不是乳酸，抑制甲酰甲硫氨酰-亮氨酰-苯丙氨酸（fMLP）刺激的PMN极化，F-肌动蛋白定位，和细胞质pH值振荡。丙酸盐诱导的细胞骨架F-肌动蛋白和细胞质酸化的变化不受fMLP受体拮抗剂N-t-BOC-1-甲硫氨酰-1-亮氨酰-1-苯丙氨酸的影响;然而，碱化受到影响。百日咳毒素治疗完全抑制丙酸诱导的F-肌动蛋白的变化，但丙酸诱导的细胞质pH振荡没有影响。这些结果表明，丙酸（i）绕过fMLP受体和G蛋白诱导细胞质pH振荡，（ii）通过G蛋白诱导肌动蛋白振荡，细胞形状变化（不规则）和F-肌动蛋白定位，（iii）抑制fMLP刺激的细胞质pH和肌动蛋白振荡，PMN极化和F-肌动蛋白定位。
Short-chain carboxylic acids (SCCA) are metabolic by-products of bacterial pathogens which can alter cytoplasmic pH and inhibit a variety of polymorphonuclear leukocyte (PMN) motile functions. Since cytoskeletal F-actin alterations are central to PMN mobility, in this study we examined the effects of SCCA on cytoskeletal F-actin. Initially, we tested nine SCCA (formate, acetate, propionate, butyrate, valerate, caproate, lactate, succinate, and isobutyrate). We document here that while eight altered cytoplasmic pH, only six altered cytoskeletal F-actin. We then selected one SCCA that altered both F-actin and cytoplasmic pH (propionate) and one SCCA that altered only cytoplasmic pH (lactate) for further study. Propionate, hut not lactate, caused an irregular cell shape and F-actin distribution. Furthermore, propionate, but not lactate, inhibited formylmethionyl-leucyl-phenylalanine (fMLP)-stimulated PMN polarization, F-actin localization, and cytoplasmic pH oscillation. Propionate-induced changes in cytoskeletal F-actin and cytoplasmic acidification were not affected by the fMLP receptor antagonist N-t-BOC-1-methionyl-1-leucyl-1-phenylalanine; however, alkalinization was affected. Pertussis toxin treatment completely inhibited propionate-induced changes in F-actin but had no effect on propionate-induced cytoplasmic pH oscillation. These results indicate that propionate (i) bypasses the fMLP receptor and G protein(s) to induce cytoplasmic pH oscillation, (ii) operates through G protein(s) to induce actin oscillation, cell shape changes (to irregular), and F-actin localization, and (iii) inhibits fMLP-stimulated cytoplasmic pH and actin oscillation, PMN polarization, and F-actin localization.