Cabral G A, Fischer-Stenger K
Department of Microbiology and Immunology, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298-0678.
Life Sci. 1994;54(23):1831-44. doi: 10.1016/0024-3205(94)90122-8.
Macrophages have been shown to undergo a sequential process to full activation in response to priming and triggering signals such as gamma interferon (IFN gamma) and bacterial lipopolysaccharide (LPS). These cells also may be driven directly to full activation by exposure to relatively high concentrations of LPS. Each of the stages to activation is associated with differential protein expression suggesting that newly synthesized proteins are associated with the functional activities attributable to that activation state. These observations indicate that protein profiles may serve as a barometer of the macrophage activation state. Delta-9-tetrahydrocannabinol (THC), the major psychoactive component in marijuana, was shown to inhibit inducible protein expression in response to the priming agents Concanavalin A (Con A) supernatant and IFN gamma. THC also suppressed protein expression in response to LPS. P388D1 and RAW264.7 macrophage-like cells, treated with Con A supernatant or IFN gamma, exhibited restructuring of protein profiles based on iso-Dalt two-dimensional gel electrophoresis. Protein profile restructuring, distinctive from that elicited in response to priming agents, was seen for macrophages treated with LPS. Treatment of macrophages with Con A supernatant, IFN gamma, or LPS in concert with THC (10(-7) M to 10(-5) M), resulted in the generation of protein profiles whose patterns reverted approximately to those of unprimed or unactivated macrophages. THC was shown to alter the expression of select proteins whose induction is associated with macrophage priming or activation. The expression of P388D1 macrophage class II Ia molecules of the major histocompatibility complex (MHC), in response to Con A supernatant and IFN gamma, was inhibited. THC also altered the expression of tumor necrosis factor alpha (TNF alpha) elicited by RAW264.7 cells in response to LPS. These results suggest that THC alters macrophage functional activities, at least in part, by suppressing their capacity to express effector molecules elicited in response to priming and activating signals.
巨噬细胞已被证明会经历一个顺序过程以响应诸如γ干扰素（IFNγ）和细菌脂多糖（LPS）等引发和触发信号而完全激活。这些细胞也可能通过暴露于相对高浓度的LPS而直接被驱动至完全激活。激活的每个阶段都与差异蛋白表达相关，这表明新合成的蛋白质与该激活状态下的功能活动相关。这些观察结果表明蛋白质谱可能作为巨噬细胞激活状态的晴雨表。Δ-9-四氢大麻酚（THC）是大麻中的主要精神活性成分，已被证明可抑制对引发剂刀豆球蛋白A（Con A）上清液和IFNγ的诱导蛋白表达。THC还抑制对LPS的蛋白表达。用Con A上清液或IFNγ处理的P388D1和RAW264.7巨噬细胞样细胞，基于等密度双相二维凝胶电泳显示出蛋白质谱的重组。在用LPS处理的巨噬细胞中观察到与对引发剂反应所引发的不同的蛋白质谱重组。用Con A上清液、IFNγ或LPS与THC（10⁻⁷M至10⁻⁵M）协同处理巨噬细胞，导致产生的蛋白质谱模式大约恢复到未引发或未激活巨噬细胞的模式。THC被证明会改变某些蛋白质的表达，这些蛋白质的诱导与巨噬细胞引发或激活有关。主要组织相容性复合体（MHC）的P388D1巨噬细胞II类Ia分子在对Con A上清液和IFNγ反应时的表达受到抑制。THC还改变了RAW264.7细胞对LPS反应所引发的肿瘤坏死因子α（TNFα）的表达。这些结果表明THC至少部分地通过抑制巨噬细胞表达对引发和激活信号作出反应所引发的效应分子的能力来改变巨噬细胞的功能活动。
