Brummer E, Gilmore G L, Shadduck R K, Stevens D A
Department of Medicine, Santa Clara Valley Medical Center, and California Institute for Medical Research, San Jose, California, 95128, USA.
Cell Immunol. 1998 Nov 1;189(2):144-8. doi: 10.1006/cimm.1998.1366.
We previously showed that nonactivated resident murine peritoneal macrophages (PM) from five strains (e.g., BALB/c) have C'-dependent fungistasis for Cryptococcus neoformans in 24-h coculture, but not CD-1 PM unless culture time was extended or M-CSF treatment was used. We studied effect of a rat IgG1 monoclonal (m) antibody (Ab) to murine M-CSF receptor on this anticryptococal activity. Culture of BALB/c PM with mAb, diluted 1:10, prechallenge reduced fungistasis from 58 to 21% (P < 0.01), whereas further 10-fold dilutions did not. Moreover, M-CSF pretreatment (5000 U/ml) significantly enhanced fungistasis (to 85%), whereas adding mAb 1:10 or 1:100 reduced that (to 58 and 77%, respectively, P < 0.01). In 48-h culture CD-1 PM had 39% fungistasis, reduced to 0% by mAb, M-CSF treatment of CD-1 PM increased fungistasis to 72%, which was reduced to 13 or 58% (P < 0. 001) by 1:10 or 1:100 mAb, respectively. Complete blocking by mAb of CD-1 PM activity was consistent with lack of measurable early endogenous CD-1 M-CSF production. Increasing exogenous M-CSF could overcome the inhibition by mAb (64% fungistasis BALB/c PM reduced to 11% with inhibition by mAb or increased to 94% with 5000 U/ml M-CSF; 37% with both mAb and M-CSF, 51% with mAb and 10,000 U/ml; P < 0.05, 5000 U/ml + mAb vs 10,000 U/ml + mAb). Moreover, rabbit Ab to M-CSF significantly reduced anticryptococcal activity of untreated BALB/c macrophages. In summary, development of PM fugistatic activity is dependent on endogenous M-CSF, since it is blocked by anti-receptor mAb (as is exogenous M-CSF stimulation) or anti-M-CSF Ab, and macrophages of the mouse strain with delayed activity had no measurable early M-CSF production.
我们先前表明，来自五个品系（如BALB/c）的未活化的驻留小鼠腹腔巨噬细胞（PM）在24小时共培养中对新型隐球菌具有补体（C）依赖性抑菌作用，但CD-1 PM则不然，除非延长培养时间或使用M-CSF处理。我们研究了一种针对小鼠M-CSF受体的大鼠IgG1单克隆（m）抗体（Ab）对这种抗隐球菌活性的影响。用稀释至1:10的mAb预刺激培养BALB/c PM，可使抑菌作用从58%降至21%（P<0.01），而进一步10倍稀释则无此效果。此外，M-CSF预处理（5000 U/ml）可显著增强抑菌作用（至85%），而加入1:10或1:100的mAb则会降低抑菌作用（分别降至58%和77%，P<0.01）。在48小时培养中，CD-1 PM的抑菌率为39%，mAb可将其降至0%，M-CSF处理CD-1 PM可使抑菌率提高至72%，1:10或1:100的mAb分别将其降至13%或58%（P<0.001）。mAb对CD-1 PM活性的完全阻断与缺乏可测量的早期内源性CD-1 M-CSF产生一致。增加外源性M-CSF可克服mAb的抑制作用（BALB/c PM的抑菌率从64%降至mAb抑制时的11%，或在5000 U/ml M-CSF时提高至94%；mAb和M-CSF同时存在时为37%，mAb和10000 U/ml时为51%；P<0.05，5000 U/ml + mAb与10000 U/ml + mAb相比）。此外，抗M-CSF兔Ab可显著降低未处理的BALB/c巨噬细胞的抗隐球菌活性。总之，PM抑菌活性的发展依赖于内源性M-CSF，因为它可被抗受体mAb（外源性M-CSF刺激也如此）或抗M-CSF Ab阻断，且活性延迟的小鼠品系的巨噬细胞没有可测量的早期M-CSF产生。
