Mates Jessica M, Yao Zhili, Cheplowitz Alana M, Suer Ozan, Phillips Gary S, Kwiek Jesse J, Rajaram Murugesan V S, Kim Jonghan, Robinson John M, Ganesan Latha P, Anderson Clark L
Departments of Internal Medicine, The Ohio State University , Columbus, OH , USA.
Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University , Columbus, OH , USA.
Front Immunol. 2017 Jan 24;8:35. doi: 10.3389/fimmu.2017.00035. eCollection 2017.
We crafted human immunodeficiency virus (HIV)-like particles of diameter about 140 nm, which expressed two major HIV-1 proteins, namely, and gene products, and used this reagent to simulate the rate of decay of HIV from the blood stream of BALB/c male mice. We found that most (~90%) of the particles were eliminated (cleared) from the blood by the liver sinusoidal endothelial cells (LSECs), the remainder from Kupffer cells; suggesting that LSECs are the major liver scavengers for HIV clearance from blood. Decay was rapid with kinetics suggesting second order with respect to particles, which infers dimerization of a putative receptor on LSEC. The number of HIV-like particles required for saturating the clearance mechanism was approximated. The capacity for elimination of blood-borne HIV-like particles by the sinusoid was 112 million particles per minute. Assuming that the sinusoid endothelial cells were about the size of glass-adherent macrophages, then elimination capacity was more than 540 particles per hour per endothelial cell.
我们制备了直径约140纳米的人类免疫缺陷病毒(HIV)样颗粒,其表达两种主要的HIV-1蛋白,即 和 基因产物,并使用该试剂模拟HIV从BALB/c雄性小鼠血流中的衰减速率。我们发现,大多数(约90%)颗粒被肝窦内皮细胞(LSEC)从血液中清除,其余的被库普弗细胞清除;这表明LSEC是肝脏中从血液清除HIV的主要清除细胞。衰减很快,动力学表明与颗粒呈二级关系,这推断LSEC上一种假定受体的二聚化。估算了饱和清除机制所需的HIV样颗粒数量。肝窦每分钟清除血源HIV样颗粒的能力为1.12亿个颗粒。假设肝窦内皮细胞大小与贴壁巨噬细胞相近,那么每个内皮细胞每小时的清除能力超过540个颗粒。