Department of Pneumonology, Medical University of Gdansk, Debinki 7 Str., 80-211 Gdansk, Poland.
Hum Immunol. 2012 Aug;73(8):788-94. doi: 10.1016/j.humimm.2012.05.005. Epub 2012 May 15.
We have recently revealed that mycobacterial heat shock proteins (Mtb-hsp), involved in forming of immune complexes (CIs), can induce immune response in sarcoidosis (SA). The complexemia may result from inappropriate phagocytosis and clearance of CIs by monocytes with following persistent antigenemia and granuloma formation. Because an aberrant expression of receptors for Fc fragment of immunoglobulin G (FcγR) and complement receptors (CR) on monocytes can be involved in this process, we have evaluated the expression of FcγRI (CD64), FcγRII (CD32), FcγRIII (CD16) and CR1 (CD35), CR3 (CD11b), CR4 (CD11c) receptors on blood CD14(+) monocytes and its phagocytic activity in 24 patients with SA and 20 healthy volunteers using flow cytometry. We found significantly increased expression of all examined FcγR and decreased expression of CD35 and CD11c on CD14(+) monocytes in SA patients vs controls. Significantly increased percentage of CD14(+)CD16(+)CD35(-), CD14(+)CD64(+)CD35(+), CD14(+)CD64(+)CD11b(+), CD14(+)CD64(+)CD11c(+) and decreased of CD14(+)CD32(-)CD35(+), CD14(+)CD32(-)CD11b(+), CD14(+)CD32(-)CD11c(+) monocytes' phenotypes was revealed in SA. The total number and percentage of phagocyting monocytes was significantly increased in SA as compared with controls. In conclusion, altered expression of FcγR and CR on CD14(+) monocytes and its increased phagocytic activity may be responsible for high antigen load, persistent antigenemia and immunocomplexemia in SA patients.
我们最近发现,与免疫复合物(CIs)形成有关的分枝杆菌热休克蛋白(Mtb-hsp)可在结节病(SA)中诱导免疫反应。复合物血症可能是由于单核细胞吞噬和清除 CIs 不当,随后持续的抗原血症和肉芽肿形成所致。因为单核细胞上的免疫球蛋白 G(IgG)Fc 片段受体(FcγR)和补体受体(CR)的异常表达可能参与这一过程,我们评估了 CD14+单核细胞上 FcγRI(CD64)、FcγRII(CD32)、FcγRIII(CD16)和 CR1(CD35)、CR3(CD11b)、CR4(CD11c)受体的表达及其吞噬活性在 24 例 SA 患者和 20 名健康志愿者中,使用流式细胞术。我们发现,与对照组相比,SA 患者 CD14+单核细胞上所有检测到的 FcγR 表达显著增加,CD35 和 CD11c 表达降低。CD14+CD16+CD35-、CD14+CD64+CD35+、CD14+CD64+CD11b+、CD14+CD64+CD11c+单核细胞的比例显著增加,而 CD14+CD32-CD35+、CD14+CD32-CD11b+、CD14+CD32-CD11c+单核细胞表型的比例降低。与对照组相比,SA 患者的吞噬单核细胞总数和百分比显著增加。总之,CD14+单核细胞上 FcγR 和 CR 的表达改变及其吞噬活性的增加可能是 SA 患者高抗原负荷、持续抗原血症和免疫复合物血症的原因。