Xing Dongqi, Hage Fadi G, Chen Yiu-Fai, McCrory Mark A, Feng Wenguang, Skibinski Gregory A, Majid-Hassan Erum, Oparil Suzanne, Szalai Alexander J
Vascular Biology and Hypertension Program, The University of Alabama at Birmingham, Birmingham, Alabama, USA.
Am J Pathol. 2008 Jan;172(1):22-30. doi: 10.2353/ajpath.2008.070154. Epub 2007 Dec 6.
Neointima formation after vascular injury is exaggerated in ovariectomized (OVX) human C-reactive protein transgenic mice (CRPtg) compared to nontransgenic mice (NTG). We tested the hypothesis that this CRP-mediated exacerbation requires IgG Fc receptors (Fc gamma Rs). OVX NTG, CRPtg, and CRPtg lacking Fc gamma RI, Fc gamma RIIb, Fc gamma RIII, or the common gamma chain (FcR gamma) had their common carotid artery ligated. Twenty-eight days later neointimal thickening in CRPtg/Fc gamma RI(-/-) and CRPtg/FcR gamma (-/-) was significantly less than in CRPtg and no worse than in NTG, whereas in CRPtg/Fc gamma RIIb(-/-) and CRPtg/Fc gamma RIII(-/-) neointimal thickness was equal to or greater than in CRPtg. Immunohistochemistry revealed human CRP in the neointima of CRPtg, but little or none was observed in those lacking Fc gamma RI or FcR gamma. Real-time reverse transcriptase-polymerase chain reaction demonstrated that Fc gamma R types I to III were expressed in the CRPtg arteries, with Fc gamma RI expression increasing by threefold after ligation injury. Levels of serum complement (C3), neointimal deposition of complement (C3d), and cellular composition (monocytes, macrophages, lymphocytes) in the neointima did not differ among the different CRPtg genotypes. However, by immunofluorescence a neointimal population of F4/80+CRP+ cells was revealed only in OVX CRPtg. The exaggerated response to vascular injury provoked by CRP in OVX CRPtg depends on Fc gamma RI and probably requires its expression by F4/80+ cells.
与非转基因小鼠（NTG）相比，去卵巢（OVX）的人C反应蛋白转基因小鼠（CRPtg）血管损伤后新生内膜形成更为严重。我们验证了这一假说，即这种由CRP介导的病情加重需要IgG Fc受体（FcγRs）。对OVX NTG、CRPtg以及缺乏FcγRI、FcγRIIb、FcγRIII或共同γ链（FcRγ）的CRPtg小鼠进行颈总动脉结扎。28天后，CRPtg/FcγRI（-/-）和CRPtg/FcRγ（-/-）小鼠的新生内膜增厚明显小于CRPtg小鼠，且不比NTG小鼠严重；而CRPtg/FcγRIIb（-/-）和CRPtg/FcγRIII（-/-）小鼠的新生内膜厚度等于或大于CRPtg小鼠。免疫组织化学显示CRPtg小鼠新生内膜中有人类CRP，但在缺乏FcγRI或FcRγ的小鼠中几乎未观察到或未观察到CRP。实时逆转录聚合酶链反应表明，FcγR I至III型在CRPtg小鼠动脉中表达，结扎损伤后FcγRI表达增加了三倍。不同CRPtg基因型小鼠的血清补体（C3）水平、补体在新生内膜中的沉积（C3d）以及新生内膜中的细胞组成（单核细胞、巨噬细胞、淋巴细胞）并无差异。然而，通过免疫荧光法仅在OVX CRPtg小鼠中发现了F4/80+CRP+细胞的新生内膜群体。CRP在OVX CRPtg小鼠中引发的对血管损伤的过度反应依赖于FcγRI，可能需要F4/80+细胞表达该受体。
