Ouyang Guan-Feng, Saio Masanao, Suwa Tatsuhiko, Imai Hisashi, Nakagawa Jiro, Nonaka Kenichi, Umemura Naoki, Kijima Mika, Takami Tsuyoshi
Department of Immunopathology, Gifu University Graduate School of Medicine, Yanagido, Gifu, Japan.
Int J Oncol. 2006 May;28(5):1201-8.
The contribution of tumor associated macrophage (TAM) to the induction of major histocompatibility complex (MHC) class I expression in vivo has not been reported precisely. In this study, we utilized Interleukin-2 (IL-2) cDNA-introduced B16 melanoma cells (B16/IL-2) and vehicle-alone control cells (B16/mock) to examine whether TAM could contribute to the induction of MHC class I on B16 cells in vivo. Interestingly, although B16/mock and B16/IL-2 did not express MHC class I in vitro, MHC class I was strongly expressed in vivo in B16/IL-2 in comparison to B16/mock. Although in vivo treatment of anti-NK1.1 antibody abolished MHC expression in B16/mock in vivo, the same treatment did not influence MHC expression in B16/IL-2. Interestingly, both anti-asialo GM1 and anti-CD11b treatment strongly decreased MHC expression in B16/IL-2. TAM expressed both asialo GM1 and CD11b antigen, and TAM recovered from B16/IL-2 produced interferon gamma (IFNgamma) 6 times more than that from B16/mock. In addition, TAM recovered from B16/IL-2 secreted 33.64 times more IFNgamma in response to in vitro administration of IL-2. Therefore, we checked whether or not IL-2 could influence the expression of IL-2 receptors. TAM recovered from IL-2 expressed middle affinity receptor of IL-2 (CD122 and CD132) while that from B16/mock expressed low affinity receptor (CD25 and CD132). Finally, we observed that B16 cells became apoptotic with IFNgamma treatment in vitro. These results suggested that IL-2 augmented activation of TAM would play the main role in induction of the MHC class I molecule through secretion of IFNgamma, and would contribute to the IFNgamma-mediated apoptosis induction in tumor cells.
肿瘤相关巨噬细胞（TAM）对体内主要组织相容性复合体（MHC）I类分子表达的诱导作用尚未得到确切报道。在本研究中，我们利用导入白细胞介素-2（IL-2）cDNA的B16黑色素瘤细胞（B16/IL-2）和仅用载体处理的对照细胞（B16/ mock），来检测TAM是否能在体内促进B16细胞上MHC I类分子的诱导表达。有趣的是，尽管B16/ mock和B16/IL-2在体外均不表达MHC I类分子，但与B16/ mock相比，B16/IL-2在体内却强烈表达MHC I类分子。虽然体内给予抗NK1.1抗体可消除B16/ mock体内的MHC表达，但相同处理对B16/IL-2的MHC表达并无影响。有趣的是，抗去唾液酸GM-1和抗CD11b处理均能显著降低B16/IL-2中的MHC表达。TAM表达去唾液酸GM-1和CD11b抗原，从B16/IL-2中分离得到的TAM产生的干扰素γ（IFNγ）比从B16/ mock中分离得到的多6倍。此外，体外给予IL-2后，从B16/IL-2中分离得到的TAM分泌的IFNγ比从B16/ mock中分离得到的多33.64倍。因此，我们检测了IL-2是否会影响IL-2受体的表达。从IL-2中分离得到的TAM表达IL-2的中亲和力受体（CD122和CD132），而从B16/ mock中分离得到的TAM表达低亲和力受体（CD25和CD132）。最后，我们观察到体外给予IFNγ处理后B16细胞发生凋亡。这些结果表明，IL-2增强的TAM活化通过分泌IFNγ在诱导MHC I类分子表达中起主要作用，并有助于IFNγ介导的肿瘤细胞凋亡诱导。
