Effects of HIV-1 infection in vitro on transendothelial migration by monocytes and monocyte-derived macrophages

被引:33
|
作者
Westhorpe, Clare L. V. [1 ,2 ]
Zhou, Jingling [1 ]
Webster, Nicole L. [3 ]
Kalionis, Bill [4 ,5 ,6 ]
Lewin, Sharon R. [1 ,2 ,7 ]
Jaworowski, Anthony [1 ,2 ]
Muller, William A. [8 ]
Crowe, Suzanne M. [1 ,2 ]
机构
[1] Macfarlane Burnet Inst Med Res & Publ Hlth, Ctr Virol, Melbourne, Vic 3001, Australia
[2] Monash Univ, Dept Med, Melbourne, Vic 3004, Australia
[3] Univ Melbourne, Dept Microbiol & Immunol, Melbourne, Vic, Australia
[4] Royal Womens Hosp, Dept Perinatal Med, Pregnancy Res Ctr, Carlton, Vic, Australia
[5] Royal Womens Hosp, Dept Obstet & Gynaecol, Carlton, Vic, Australia
[6] Univ Melbourne, Carlton, Vic 3053, Australia
[7] Monash Univ, Alfred Hosp, Infect Dis Unit, Melbourne, Vic 3181, Australia
[8] Northwestern Univ, Dept Pathol, Chicago, IL 60611 USA
基金
英国医学研究理事会;
关键词
cells of macrophage lineage; CCR8; HUVEC; innate immunity; COMPLEMENT-MEDIATED PHAGOCYTOSIS; HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN PERIPHERAL-BLOOD; DENDRITIC CELLS; MONONUCLEAR PHAGOCYTES; ALVEOLAR MACROPHAGES; VASCULAR ENDOTHELIUM; ADHESION MOLECULES; FLOW CONDITIONS; LYMPH-NODES;
D O I
10.1189/jlb.0808501
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Monocytes constitutively migrate from the bloodstream across the vascular endothelium for systemic immune surveillance and maintenance of macrophage populations. They also perform reverse transendothelial migration (TEM) across the endothelium, which is required for entry of tissue monocytes/macrophages into the lymphatics or back into the bloodstream. We have modeled these processes previously using HUVEC monolayers grown on threedimensional collagen matrices. The aim of the present study was to determine whether HIV-1 infection of monocytes/macrophages in vitro affects TEM. Purified primary human monocytes and monocyte-derived macrophages (MDM) expressed important TEM proteins such as CD62L, CD18, PECAM-1, CCR2, and CCR8. Purified monocytes underwent efficient forward and reverse TEM across HUVEC, and this function was maintained by MDM after up to 15 days of culture. Monocytes exposed to HIV- 1 for 2 days had unaltered forward or reverse TEM. However, HIV-1 infection of MDM for 7 days decreased reverse TEM by an average of 66.5% compared with mock-infected MDM (n = 9 independent donors; P = 0.004), without affecting forward TEM. Decreased reverse TEM by HIV-infected MDM required viral RT and was not a result of alterations in surface expression of CCR8 or p-glycoprotein or a general impairment in mobility, as assessed by migration toward fMLP. This study indicates that HIV-1 infection of macrophages reduces their capacity to emigrate from the subendothelial extracellular matrix in vitro, which could result in defective cell-mediated immune responses to infections and promote establishment of viral reservoirs of HIV in tissue macrophages in vivo. J. Leukoc. Biol. 85: 1027-1035; 2009.
引用
收藏
页码:1027 / 1035
页数:9
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