期刊
JOURNAL OF LEUKOCYTE BIOLOGY
卷 80, 期 5, 页码 1165-1174出版社
WILEY
DOI: 10.1189/jlb.0206110
关键词
monocytes; cell trafficking; mouse; indinavir
资金
- NCRR NIH HHS [P20 RR15635] Funding Source: Medline
- NIAID NIH HHS [P30 AI42845] Funding Source: Medline
- NIMH NIH HHS [P01 MH64570] Funding Source: Medline
- NINDS NIH HHS [P01 NS31492, P01 NS11766, R01 NS34239, NS 43011, R37 NS36126, P01 NS43985, T32 NS07488] Funding Source: Medline
- PHS HHS [R1049264] Funding Source: Medline
We posit that the same mononuclear phagocytes (MP) [bone marrow (BM) and blood monocytes, tissue macrophages, microglia, and dendritic cells] which serve as targets, reservoirs, and vehicles for HIV dissemination, can be used as vehicles for antiretroviral therapy (ART). Toward this end, BM macrophages (BMM) were used as carriers for nanoparticle-formulated indinavir (NP-IDV), and the cell distribution was monitored by single photon emission computed tomography (SPECT), transverse relation time (T-2)* weighted magnetic resonance imaging (MRI), histology, and T-scintillation spectrometry. BMM labeled with super paramagnetic iron oxide and/or (111)indium oxine were infused i.v. into naive mice. During the first 7 h, greater than 86% of cell label was recorded within the lungs. On Days 1, 3, 5, and 7, less than 10% of BMM were in lungs, and 74-81% and 13-18% were in liver and spleen, respectively. On a tissue volume basis, as determined by SPECT and MRI, BMM densities in spleen and liver were significantly greater than other tissues. Migration into the lymph nodes on Days I and 7 accounted for 1.5-2% of the total BMM. Adoptive transfer of BMM loaded with NP-IDV produced drug levels in lymphoid and nonlymphoid tissues that exceeded reported therapeutic concentrations by 200- to 350-fold on Day 1 and remained in excess of 100- to 300-fold on Day 14. These data show real-time kinetics and destinations of macrophage trafficking and demonstrate the feasibility of monitoring macrophage-based, nanoformulated ART. J. Leukoc. Biol. 80: 1165-1174; 2006.
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