Technical Advance: Liposomal alendronate depletes monocytes and macrophages in the nonhuman primate model of human disease
| Autor: | Shannon L. Planer, Katherine B. Hammond, Benjamin J. Burwitz, Jonah B. Sacha, Merete A. Ohme, Adam J. Ericsen, Yoram Richter, Alfred W. Legasse, Gershon Golomb, Jason S. Reed |
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| Rok vydání: | 2014 |
| Předmět: |
DNA Replication
Immunology Drug Evaluation Preclinical Cell Count Cell Separation Biology Monocytes Flow cytometry Pathogenesis Immune system Bone Marrow Cell Movement In vivo medicine Animals Humans Immunology and Allergy Macrophage Myeloid Cells Alendronate medicine.diagnostic_test Macrophages Monocyte Cell Biology Flow Cytometry Macaca mulatta Disease Models Animal medicine.anatomical_structure Technical Advance Injections Intravenous Liposomes Bone marrow Injections Intraperitoneal Ex vivo |
| Zdroj: | Journal of Leukocyte Biology |
| ISSN: | 1938-3673 0741-5400 |
| Popis: | Nonhuman primates are critical animal models for the study of human disorders and disease and offer a platform to assess the role of immune cells in pathogenesis via depletion of specific cellular subsets. However, this model is currently hindered by the lack of reagents that safely and specifically ablate myeloid cells of the monocyte/macrophage Lin. Given the central importance of macrophages in homeostasis and host immunity, development of a macrophage-depletion technique in nonhuman primates would open new avenues of research. Here, using LA at i.v. doses as low as 0.1 mg/kg, we show a >50% transient depletion of circulating monocytes and tissue-resident macrophages in RMs by an 11-color flow cytometric analysis. Diminution of monocytes was followed rapidly by emigration of monocytes from the bone marrow, leading to a rebound of monocytes to baseline levels. Importantly, LA was well-tolerated, as no adverse effects or changes in gross organ function were observed during depletion. These results advance the ex vivo study of myeloid cells by flow cytometry and pave the way for in vivo studies of monocyte/macrophage biology in nonhuman primate models of human disease. |
| Databáze: | OpenAIRE |
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