重组水蛭素和 PAR-1 调节弥漫性大 B 细胞淋巴瘤中巨噬细胞的极化状态。
Recombinant hirudin and PAR-1 regulate macrophage polarisation status in diffuse large B-cell lymphoma.
机构信息
Department of Hematology, The First People's Hospital of Yunnan Province, No. 157 of Jinbi Street, Kunming, 650032, Yunnan, China.
Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650032, Yunnan, China.
出版信息
BMC Biotechnol. 2024 Aug 12;24(1):55. doi: 10.1186/s12896-024-00879-w.
BACKGROUND
Diffuse large B-cell lymphoma (DLBCL) is a malignant tumour. Although some standard therapies have been established to improve the cure rate, they remain ineffective for specific individuals. Therefore, it is meaningful to find more novel therapeutic approaches. Macrophage polarisation is extensively involved in the process of tumour development. Recombinant hirudin (rH) affects macrophages and has been researched frequently in clinical trials lately. Our article validated the regulatory role of rH in macrophage polarisation and the mechanism of PAR-1 by collecting clinical samples and subsequently establishing a cellular model to provide a scientifically supported perspective for discovering new therapeutic approaches.
METHOD
We assessed the expression of macrophage polarisation markers, cytokines and PAR-1 in clinical samples. We established a cell model by co-culture with THP-1 and OCI-Ly10 cell. We determined the degree of cell polarisation and expression of validation cytokines by flow cytometry, ELISA, and RT-qPCR to confirm the success of the cell model. Subsequently, different doses of rH were added to discover the function of rH on cell polarisation. We confirmed the mechanism of PAR-1 in macrophage polarisation by transfecting si-PAR-1 and pcDNA3.1-PAR-1.
RESULTS
We found higher expression of M2 macrophage markers (CD163 + CMAF+) and PAR-1 in 32 DLBCL samples. After inducing monocyte differentiation into M0 macrophages and co-culturing with OCI-Ly10 lymphoma cells, we found a trend of these expressions in the cell model consistent with the clinical samples. Subsequently, we discovered that rH promotes the polarisation of M1 macrophages but inhibits the polarisation of M2 macrophages. We also found that PAR-1 regulates macrophage polarisation, inhibiting cell proliferation, migration, invasion and angiogenic capacity.
CONCLUSION
rH inhibits macrophage polarisation towards the M2 type and PAR-1 regulates polarisation, proliferation, migration, invasion, and angiogenesis of DLBCL-associated macrophages.
背景
弥漫性大 B 细胞淋巴瘤（DLBCL）是一种恶性肿瘤。尽管已经建立了一些标准疗法来提高治愈率，但对某些特定个体仍然无效。因此，寻找更多新的治疗方法是有意义的。巨噬细胞极化广泛参与肿瘤的发展过程。重组水蛭素（rH）影响巨噬细胞，最近在临床试验中得到了广泛研究。我们的文章通过收集临床样本并随后建立细胞模型，验证了 rH 对巨噬细胞极化的调节作用和 PAR-1 的作用机制，为发现新的治疗方法提供了科学依据。
方法
我们评估了临床样本中巨噬细胞极化标志物、细胞因子和 PAR-1 的表达。我们通过 THP-1 和 OCI-Ly10 细胞共培养建立了细胞模型。通过流式细胞术、ELISA 和 RT-qPCR 确定细胞极化程度和验证细胞因子的表达，以确认细胞模型的成功。随后，加入不同剂量的 rH 以发现 rH 对细胞极化的作用。通过转染 si-PAR-1 和 pcDNA3.1-PAR-1 来确认 PAR-1 在巨噬细胞极化中的作用机制。
结果
我们发现 32 例 DLBCL 样本中 M2 巨噬细胞标志物（CD163+CMAF+）和 PAR-1 的表达较高。在诱导单核细胞分化为 M0 巨噬细胞并与 OCI-Ly10 淋巴瘤细胞共培养后，我们发现细胞模型中的这些表达趋势与临床样本一致。随后，我们发现 rH 促进 M1 巨噬细胞的极化，但抑制 M2 巨噬细胞的极化。我们还发现 PAR-1 调节巨噬细胞极化，抑制细胞增殖、迁移、侵袭和血管生成能力。
结论
rH 抑制巨噬细胞向 M2 型极化，PAR-1 调节与 DLBCL 相关的巨噬细胞的极化、增殖、迁移、侵袭和血管生成。
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