Burd R S, Raymond C S, Dunn D L
Department of Surgery, University of Minnesota, Minneapolis 55455.
J Surg Res. 1992 Jun;52(6):537-42. doi: 10.1016/0022-4804(92)90125-j.
Previous studies have suggested that the lipopolysaccharide (LPS, endotoxin) component of the gram-negative bacterial cell wall is a key virulence factor that serves to enhance mortality during infections in which fungi and gram-negative bacteria are copathogens. To test this hypothesis, mice were challenged ip with Escherichia coli 0111:B4, Candida albicans, or both, and the effect of administration of anti-E. coli 0111:B4 LPS monoclonal antibody (mAb) 8G9 on endotoxemia, bacteremia, and mortality was assessed. E. coli (2 x 10(7) colony-forming units (CFU)) plus C. albicans (6 x 10(7) CFU) infection produced 100% mortality at 7 days, compared to the relatively low mortality caused by infection with either E. coli or C. albicans alone (20 and 3%, respectively, P less than 0.01). Administration of mAb 8G9 to animals receiving both pathogens reduced mortality (100% versus 14%, P less than 0.05), endotoxemia (3653 +/- 3187 versus 2 +/- 2 endotoxin units (EU), P less than 0.01), and bacteremia (4.2 +/- 2.3 versus 1.1 +/- 2.1 log(CFU/ml), P less than 0.01) compared to animals receiving saline alone. In a separate series of experiments, purified E. coli 0111:B4 LPS was administered in place of viable E. coli. The simultaneous injection of 200 micrograms E. coli LPS and C. albicans (6 x 10(7) CFU) produced 93% mortality at 7 days, compared to the low mortality that occurred following injection with either E. coli 0111:B4 LPS or C. albicans alone (21 and 3% respectively, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
先前的研究表明，革兰氏阴性菌细胞壁的脂多糖（LPS，内毒素）成分是一种关键的毒力因子，在真菌和革兰氏阴性菌作为共同病原体的感染过程中会增加死亡率。为了验证这一假设，给小鼠腹腔注射大肠杆菌0111:B4、白色念珠菌或两者，评估给予抗大肠杆菌0111:B4 LPS单克隆抗体（mAb）8G9对内毒素血症、菌血症和死亡率的影响。与单独感染大肠杆菌或白色念珠菌所导致的相对较低死亡率（分别为20%和3%，P<0.01）相比，大肠杆菌（2×10⁷菌落形成单位（CFU））加白色念珠菌（6×10⁷CFU）感染在7天时导致100%的死亡率。给同时感染两种病原体的动物注射mAb 8G9可降低死亡率（100%对14%，P<0.05）、内毒素血症（3653±3187对2±2内毒素单位（EU），P<0.01）和菌血症（4.2±2.3对1.1±2.1 log（CFU/ml），P<0.01），与单独接受生理盐水的动物相比。在另一系列实验中，用纯化的大肠杆菌0111:B4 LPS代替活的大肠杆菌进行给药。与单独注射大肠杆菌0111:B4 LPS或白色念珠菌后发生的低死亡率（分别为21%和3%，P<0.01）相比，同时注射200微克大肠杆菌LPS和白色念珠菌（6×10⁷CFU）在7天时导致93%的死亡率。（摘要截短于250字）
