de Jong D M, Pate J L, Kirkland T N, Taylor C E, Baker P J, Takayama K
Department of Bacteriology, College of Agricultural and Life Sciences, University of Wisconsin, Madison 53706.
Infect Immun. 1991 Aug;59(8):2631-7. doi: 10.1128/iai.59.8.2631-2637.1991.
Glycoproteins (GP) previously shown to be involved in the gliding motility of Cytophaga johnsonae were examined for biological activities characteristic of lipopolysaccharide (LPS). These integral membrane proteins activated 70Z/3 pre-B cells to synthesize immunoglobulin M, induced B cells to synthesize non-antigen-specific polyclonal immunoglobulin, induced macrophages to produce tumor necrosis factor, and modulated the antibody response to type III pneumococcal polysaccharide in the absence of thymus-derived (T) lymphocytes. Except for the GP activity in the 70Z/3 assay, all activities of the GP were comparable to or greater than those of LPS. No LPS was detected in the preparations of GP used or in the phenol-water extracts of C. johnsonae. The mechanism by which these GP exerted their biological activities was distinct from that of LPS, since LPS-resistant C3H/HeJ mice responded to GP. Furthermore, biologically inactive diphosphoryl lipid A obtained from nontoxic LPS of Rhodopseudomonas sphaeroides (an analog of toxic lipid A), which is an antagonist of LPS, did not block the induction of tumor necrosis factor by GP in macrophages. These results showed that the cell surface GP from C. johnsonae are potent LPS-like activators of B cells and macrophages. We suggest that these GP might be good candidates for use in developing an effective adjuvant system.
对先前已证明参与琼氏噬纤维菌滑动运动的糖蛋白(GP)进行了脂多糖(LPS)生物学活性特征的检测。这些整合膜蛋白可激活70Z/3前B细胞合成免疫球蛋白M,诱导B细胞合成非抗原特异性多克隆免疫球蛋白,诱导巨噬细胞产生肿瘤坏死因子,并在无胸腺来源(T)淋巴细胞的情况下调节对III型肺炎球菌多糖的抗体反应。除了在70Z/3检测中的GP活性外,GP的所有活性均与LPS相当或高于LPS。在所使用的GP制剂或琼氏噬纤维菌的酚水提取物中均未检测到LPS。这些GP发挥其生物学活性的机制与LPS不同,因为LPS抗性的C3H/HeJ小鼠对GP有反应。此外,从球形红假单胞菌的无毒LPS(有毒脂质A的类似物)获得的无生物学活性的二磷酸脂质A(LPS的拮抗剂)并不能阻断GP在巨噬细胞中诱导肿瘤坏死因子的产生。这些结果表明,琼氏噬纤维菌的细胞表面GP是B细胞和巨噬细胞的强效LPS样激活剂。我们认为这些GP可能是开发有效佐剂系统的良好候选物。