Published online before print December 6, 2007

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(American Journal of Pathology. 2008;172:22-30.)
© 2008 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2008.070154

Exaggerated Neointima Formation in Human C-Reactive Protein Transgenic Mice Is IgG Fc Receptor Type I (FcRI)-Dependent

Dongqi Xing^*, Fadi G. Hage^*, Yiu-Fai Chen^*, Mark A. McCrory, Wenguang Feng^*, Gregory A. Skibinski, Erum Majid-Hassan^*, Suzanne Oparil^* and Alexander J. Szalai

From the Vascular Biology and Hypertension Program,^*Division of Cardiovascular Disease, and the Department of Medicine,Division of Clinical Immunology and Rheumatology, The University of Alabama at Birmingham, Birmingham, Alabama

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 (FcRs). OVX NTG, CRPtg, and CRPtg lacking FcRI, FcRIIb, FcRIII, or the common chain (FcR) had their common carotid artery ligated. Twenty-eight days later neointimal thickening in CRPtg/FcRI^–/– and CRPtg/FcR^–/– was significantly less than in CRPtg and no worse than in NTG, whereas in CRPtg/FcRIIb^–/– and CRPtg/FcRIII^–/– 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 FcRI or FcR. Real-time reverse transcriptase-polymerase chain reaction demonstrated that FcR types I to III were expressed in the CRPtg arteries, with FcRI 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 FcRI and probably requires its expression by F4/80⁺ cells.

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