Modulation of Leishmania donovani infection and cell viability by testosterone in bone marrow-derived macrophages: signaling via surface binding sites.
Androgens can increase susceptibility toward numerous parasitic infections as well as modulate apoptosis of immune cells. According to the current view, androgens mediate immune cell activities not only through classical intracellular androgen receptors (AR), but also through membrane receptors on the cell surface. Here, using murine bone marrow-derived macrophages (BMMs), we examined the influence of testosterone on Leishmania donovani infection and cell viability in vitro as well as the possible mechanisms. Our data demonstrated that testosterone directly increased intramacrophage infection by L. donovani. In addition, testosterone decreased cell viability by way of apoptosis, accompanied by increased Fas, FasL, and Caspase-8 expression. However, these effects of testosterone could not be associated with the classical AR in BMMs since AR was not detectable using different experimental techniques. Instead, it was found that testosterone could bind to the surface of BMMs by the use of an impermeable testosterone-BSA-FITC in confocal laser scanning microscopy and flow cytometry. Collectively, our data indicated that the influence of testosterone on L. donovani infection and viability of BMMs was mediated through the binding sites of testosterone on cell surfaces, which provided a novel mode of direct action of testosterone on AR-free BMMs.
Liu
Limin
L
Medical School, Shanghai Jiaotong University, Huashanlu 1954, 200030 Shanghai, PR China.
Benten
W Peter M
WP
Wang
Lianyun
L
Hao
Xiangfang
X
Li
Qiaoli
Q
Zhang
Huaping
H
Guo
Dongxing
D
Wang
Yajing
Y
Wunderlich
Frank
F
Qiao
Zhongdong
Z
D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis; D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites; D001854:Bone Marrow Cells / Q000166:cytology*; D053181:Caspase 8; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D053222:Fas Ligand Protein; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007893:Leishmania donovani / Q000382:microbiology*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011944:Receptors, Androgen / Q000032:analysis; D015398:Signal Transduction / Q000502:physiology*; D013739:Testosterone / Q000494:pharmacology*; D048069:Tumor Necrosis Factors / Q000235:genetics / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
D000943:Antigens, Differentiation; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D011944:Receptors, Androgen; D048069:Tumor Necrosis Factors; D019014:fas Receptor; C036763:monocyte-macrophage differentiation antigen; D013739:Testosterone; D004958:Estradiol; D016173:Macrophage Colony-Stimulating Factor; C505526:Casp8 protein, mouse; D053181:Caspase 8; D020169:Caspases