Laberge S, Cruikshank W W, Kornfeld H, Center D M
Pulmonary Center, Boston University School of Medicine, MA 02118, USA.
J Immunol. 1995 Sep 15;155(6):2902-10.
We have reported previously that histamine induces the release of the CD4+ cell-specific lymphocyte chemoattractant factor (LCF) into the culture supernatants of CD8+ cells between 1 and 4 h following stimulation. To determine the mechanism of histamine-induced secretion of LCF, we evaluated the effects of inhibitors of gene transcription and translation on LCF production, and determined the effects of histamine stimulation on LCF mRNA induction and stability. The histamine-induced secretion of LCF from CD8+ cells was not associated with de novo synthesis of protein, nor did histamine have an effect on the induction or stability of LCF mRNA. Biologically active LCF was found in cell lysates of unstimulated CD8+ but not CD4+ T cells; however, LCF mRNA was detected at similar levels in both cell types. The only detectable lymphocyte chemoattractant present in unstimulated cells was LCF, and histamine induced the secretion of LCF, but no other lymphocyte chemoattractant activities, within 4 h. These studies demonstrate that histamine can act as a secretagogue for the protein LCF, which is constitutively synthesized and present in a biologically active form in CD8+ T cells. The rapid appearance of LCF induced by histamine may represent a mechanism for recruitment and activation for CD4+ cells in diseases such as asthma.
我们之前曾报道,组胺在刺激后1至4小时内可诱导CD4⁺细胞特异性淋巴细胞趋化因子(LCF)释放到CD8⁺细胞的培养上清液中。为了确定组胺诱导LCF分泌的机制,我们评估了基因转录和翻译抑制剂对LCF产生的影响,并确定了组胺刺激对LCF mRNA诱导和稳定性的影响。组胺诱导CD8⁺细胞分泌LCF与蛋白质的从头合成无关,组胺对LCF mRNA的诱导或稳定性也没有影响。在未刺激的CD8⁺而非CD4⁺T细胞的细胞裂解物中发现了具有生物活性的LCF;然而,在两种细胞类型中检测到的LCF mRNA水平相似。未刺激细胞中唯一可检测到的淋巴细胞趋化因子是LCF,组胺在4小时内诱导了LCF的分泌,但没有诱导其他淋巴细胞趋化因子活性。这些研究表明,组胺可作为蛋白质LCF的促分泌剂,LCF在CD8⁺T细胞中组成性合成并以生物活性形式存在。组胺诱导的LCF快速出现可能代表了哮喘等疾病中CD4⁺细胞募集和激活的一种机制。