Rao K M
Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia, USA.
J Leukoc Biol. 2001 Jan;69(1):3-10.
Stimulation of macrophages by a variety of agents causes activation of mitogen-activated protein kinases (MAPKs). Activation of MAPKs by lipopolysaccharide involves CD14 and Toll receptors. Subsequent steps still remain to be explored. Tumor necrosis factor-alpha (TNF-alpha)-induced activation of MAPKs has been shown to involve the death domain proteins (TRADD, FADD, MADD) and TRAFs. Other molecules involved in this pathway include the protein kinases, ASK1, germinal center kinase (GCK), hematopoietic progenitor kinase 1 (HPK1), and GCK-related kinase (GCKR). Although, these pathways have been described in various cell types, their role in macrophages remains to be established. The availability of knockout mice and constitutively active and dominant-negative mutants of MAPKs should greatly enhance our understanding of this field. The activation of MAPKs seems to be different in cell lines compared with primary cells. Among the macrophages, cells from different compartments show different expression of receptors and signal transduction molecules. These differences may account for differences in MAPK activation and other phenotypic differences in macrophages from different compartments. Therefore, it is important to use primary cells for studying MAPK signal-transduction pathways, and the data from cell lines should not be extrapolated to primary cells.
多种因子刺激巨噬细胞可导致丝裂原活化蛋白激酶（MAPK）激活。脂多糖激活MAPK涉及CD14和Toll受体。后续步骤仍有待探索。肿瘤坏死因子-α（TNF-α）诱导的MAPK激活已显示涉及死亡结构域蛋白（TRADD、FADD、MADD）和TRAFs。该途径中涉及的其他分子包括蛋白激酶ASK1、生发中心激酶（GCK）、造血祖细胞激酶1（HPK1）和GCK相关激酶（GCKR）。尽管这些途径已在多种细胞类型中被描述，但其在巨噬细胞中的作用仍有待确定。基因敲除小鼠以及MAPK的组成型活性和显性负性突变体的可得性应能极大地增进我们对该领域的理解。与原代细胞相比，MAPK在细胞系中的激活情况似乎有所不同。在巨噬细胞中，来自不同区室的细胞显示出不同的受体和信号转导分子表达。这些差异可能解释了不同区室巨噬细胞中MAPK激活的差异以及其他表型差异。因此，使用原代细胞研究MAPK信号转导途径很重要，细胞系的数据不应外推至原代细胞。
