Kalter D C, Nakamura M, Turpin J A, Baca L M, Hoover D L, Dieffenbach C, Ralph P, Gendelman H E, Meltzer M S
Department of Cellular Immunology, Walter Reed Army Institute of Research, Washington, DC 20307.
J Immunol. 1991 Jan 1;146(1):298-306.
Monocytes cultured 7 to 10 days in recombinant human macrophage CSF (MCSF) were greater than 400-fold more susceptible to HIV infection than an equal number of cells cultured in medium alone. Levels of reverse transcriptase activity and p24 Ag in culture fluids of monocytes treated with MCSF 1 wk before and continuously after HIV infection were significantly greater than those of control cells cultured without MCSF. HIV-induced cytopathic effects in the MCSF-treated cultures also increased in both frequency and extent. At any given viral inoculum, the frequency of HIV-infected cells, the level of HIV mRNA/infected cell, and the level of proviral DNA/infected culture in MCSF-treated monocyte cultures were dramatically greater than those in control cultures. These differences were directly related to MCSF concentration to a maximum between 750 and 1000 U/ml MCSF, and were evident at all time points examined through 5 wk. None of the preceding effects was observed when MCSF was added at the time of or 1 wk after HIV infection. These data suggest that the predominant effect of MCSF for control of HIV infection is on the monocyte itself, not the virus. If these in vitro observations extend to the HIV-infected patient, then the variable levels of MCSF in tissue or blood may determine both the susceptibility of macrophages to virus infection and the extent of virus replication in infected cells.
在重组人巨噬细胞集落刺激因子（MCSF）中培养7至10天的单核细胞，比在仅含培养基中培养的等量细胞对HIV感染的易感性高400倍以上。在HIV感染前1周及感染后持续用MCSF处理的单核细胞培养液中，逆转录酶活性水平和p24抗原水平显著高于未用MCSF培养的对照细胞。MCSF处理的培养物中HIV诱导的细胞病变效应在频率和程度上也有所增加。在任何给定的病毒接种量下，MCSF处理的单核细胞培养物中HIV感染细胞的频率、HIV mRNA/感染细胞的水平以及原病毒DNA/感染培养物的水平都显著高于对照培养物。这些差异与MCSF浓度直接相关，在750至1000 U/ml MCSF之间达到最大值，并且在整个5周的检测时间点都很明显。当在HIV感染时或感染后1周添加MCSF时，未观察到上述任何效应。这些数据表明，MCSF对HIV感染控制的主要作用是在单核细胞本身，而非病毒。如果这些体外观察结果适用于HIV感染患者，那么组织或血液中MCSF的可变水平可能既决定巨噬细胞对病毒感染的易感性，也决定病毒在感染细胞中的复制程度。
