Monocytes are differentially activated through HLA-DR, -DQ, and -DP molecules via mitogen-activated protein kinases
Monocytes are differentially activated through HLA-DR, -DQ, and -DP molecules via mitogen-activated protein kinases
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DOI：
10.4049/jimmunol.166.4.2202
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发表时间：
2001-02-15
影响因子：
4.4
通讯作者：
Matsushita, S
中科院分区：
文献类型：
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作者：
Matsuoka, T;Tabata, H;Matsushita, S
当HLA-DR，-DQ，和-DP交联的固相单克隆抗体，单核细胞产生单核细胞因子，只有抗DR显着激活丝裂原活化蛋白（MAP）激酶细胞外信号相关激酶，而抗DR，抗DQ，和抗DP都激活MAP激酶p38。细胞外信号相关激酶的激活不受TNF-α中和抗体的抑制。抗DR和DR限制性T细胞刺激单核细胞产生相对较高水平的促炎单核因子，如IL-1 β，而抗DQ/DP和DQ-/DP限制性T细胞刺激较高水平的抗炎单核因子IL-10。IL-10的产生被p38抑制剂SB 203580消除，但被MAP/细胞外信号相关激酶激酶-I特异性抑制剂PD 98059增强，而IL-1 β仅被SB 203580和PD 98059部分消除。此外，从PBMC建立的DR限制性T细胞，其与螨Ags，纯化的蛋白衍生物，和随机的19-mer肽，比DQ-或DP-限制性T细胞表现出更高的IFN-γ：IL-4比率。这些结果表明，HLA DR，-DQ和-DP分子通过MAP激酶向单核细胞传递不同的信号，并导致不同的单核因子激活模式，这可能会影响体内T细胞应答。因此，产生II类MHC的多基因家族的需要似乎是显而易见的。
When HLA-DR, -DQ, and -DP were cross-linked by solid-phase mAbs, monocytes produced monokines and only anti-DR markedly activated mitogen-activated protein (MAP) kinase extracellular signal-related kinase, whereas anti-DR, anti-DQ, and anti-DP all activated MAP kinase p38. Activation of extracellular signal-related kinase was not inhibited by neutralizing Ab to TNF-alpha. Anti-DR and DR-restricted T cells stimulated monocytes to produce relatively higher levels of proinflammatory monokines, such as IL-1 beta, whereas anti-DQ/DP and DQ-/DP-restricted T cells stimulated higher levels of anti-inflammatory monokine IL-10. IL-10 production was abrogated by the p38 inhibitor SB203580, but rather enhanced by the MAP/extracellular signal-related kinase kinase-I-specific inhibitor PD98059, whereas IL-1 beta was only partially abrogated by SB203580 and PD98059, Furthermore, DR-restricted T cells established from PBMC, which are reactive with mite Ags, purified protein derivative, and random 19-mer peptides, exhibited a higher IFN-gamma :IL-4 ratio than did DQ- or DP-restricted T cells. These results indicate that HLA DR, -DQ, and -DP molecules transmit distinct signals to monocytes via MAP kinases and lead to distinct monokine activation patterns, which may affect T cell responses in vivo. Thus, the need for generation of a multigene family of class II MHC seems apparent.