Technical advance: liposomal alendronate depletes monocytes and macrophages in the nonhuman primate model of human disease

技术进展:脂质体阿仑膦酸钠可消除人类疾病非人类灵长类动物模型中的单核细胞和巨噬细胞

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作者:Benjamin J Burwitz, Jason S Reed, Katherine B Hammond, Merete A Ohme, Shannon L Planer, Alfred W Legasse, Adam J Ericsen, Yoram Richter, Gershon Golomb, Jonah B Sacha

Abstract

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.

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