The phenotype of inflammatory macrophages is stimulus dependent: Implications for the nature of the inflammatory response
The phenotype of inflammatory macrophages is stimulus dependent: Implications for the nature of the inflammatory response
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DOI：
10.4049/jimmunol.171.9.4816
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发表时间：
2003-11-01
影响因子：
4.4
通讯作者：
Hamilton, JA
中科院分区：
文献类型：
--
作者：
Cook, AD;Braine, EL;Hamilton, JA
许多疾病的特征在于涉及免疫系统的先天和适应性臂的炎症反应。长期以来，将巯基乙酸盐培养基（TM）注射到腹膜腔中一直被用作激发炎症巨噬细胞的刺激物，用于研究和确定特定介质在炎症中的重要性。然而，对这种刺激物的反应可能与许多炎性疾病无关。因此，我们已经开发了一种Ag特异性腹膜炎模型，使用甲基化BSA（mBSA）作为刺激。用佐剂中的mBSA皮内致敏小鼠并在14天后加强免疫，然后在另外7天后用mBSA腹腔内激发，导致与TM诱导的炎症反应相当的炎症反应，如通过渗出物细胞的数量所判断的。由mBSA方案引起的炎性巨噬细胞不同，比TM引起的巨噬细胞更小且空泡化更少。此外，4天的mBSA诱导的渗出液中的巨噬细胞表达更多的MHC II类比TM诱导的渗出液，能够刺激同种异体T淋巴细胞，并在体外刺激与LPS分泌更高水平的IL-6和IL-1 β。另一方面，来自4天TM诱导的渗出物的巨噬细胞表达Ly 6C和ER-MP58，不成熟的骨髓标志物。使用Ag mBSA引起的炎症反应可能与研究许多疾病中的炎症反应更相关，例如自身免疫性疾病和涉及获得性免疫反应的疾病。
Many diseases are characterized by inflammatory reactions involving both the innate and adaptive arms of the immune system. Thioglycolate medium (TM) injection into the peritoneal cavity has long been used as a stimulus for eliciting inflammatory macrophages for study and for determining the importance of a particular mediator in inflammation. However, the response to this irritant may not be relevant to many inflammatory diseases. Therefore, we have developed an Ag-specific peritonitis model using methylated BSA (mBSA) as the stimulus. Priming mice intradermally with mBSA in adjuvant and boosting 14 days later, followed by an i.p. challenge with mBSA after an additional 7 days, led to an inflammatory reaction equivalent in magnitude to that induced with TM as judged by the number of exudate cells. The inflammatory macrophages elicited by the mBSA protocol differed, being smaller and less vacuolated than TM-elicited macrophages. Also, macrophages from 4-day mBSA-induced exudates expressed more MHC class II than TM-induced exudates, were able to stimulate allogeneic T lymphocytes, and upon in vitro stimulation with LPS secreted greater levels of IL-6 and IL-1beta. Macrophages from 4-day TM-induced exudates, on the other hand, expressed Ly6C and ER-MP58, immature myeloid markers. The inflammatory response elicited using the Ag mBSA may be more relevant for studying the inflammatory responses in many diseases, such as those of autoimmune origin and those involving an acquired immune response.