Technical advance: liposomal alendronate depletes monocytes and macrophages in the nonhuman primate model of human disease.
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.
Vaccine and Gene Therapy Institute and Division of Pathobiology and Immunology, Oregon National Primate Research Center, Oregon Health & Science University, Portland, OR, USA;
Benjamin J
BJ
Burwitz
Vaccine and Gene Therapy Institute and Division of Pathobiology and Immunology, Oregon National Primate Research Center, Oregon Health & Science University, Portland, OR, USA;
Jason S
JS
Reed
Vaccine and Gene Therapy Institute and Division of Pathobiology and Immunology, Oregon National Primate Research Center, Oregon Health & Science University, Portland, OR, USA;
Katherine B
KB
Hammond
Division of Pathobiology and Immunology, Oregon National Primate Research Center, Oregon Health & Science University, Portland, OR, USA;
Merete A
MA
Ohme
Division of Pathobiology and Immunology, Oregon National Primate Research Center, Oregon Health & Science University, Portland, OR, USA;
Shannon L
SL
Planer
Division of Pathobiology and Immunology, Oregon National Primate Research Center, Oregon Health & Science University, Portland, OR, USA;
Alfred W
AW
Legasse
Department of Pathology, University of Wisconsin-Madison, Madison, Wisconsin, USA;
Adam J
AJ
Ericsen
BioRest, Tel Aviv, Israel; and.
Yoram
Y
Richter
Institute for Drug Research, Faculty of Medicine, The Hebrew University of Jerusalem, Israel.
Gershon
G
Golomb
Vaccine and Gene Therapy Institute and Division of Pathobiology and Immunology, Oregon National Primate Research Center, Oregon Health & Science University, Portland, OR, USA; sacha@ohsu.edu.
Jonah B
JB
Sacha
D019386:Alendronate / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects; D002469:Cell Separation / Q000379:methods*; D004261:DNA Replication / Q000187:drug effects; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008081:Liposomes; D008253:Macaca mulatta / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects*; D009000:Monocytes / Q000187:drug effects*; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects
D008081:Liposomes; D019386:Alendronate
bisphosphonates; myeloid cells