Polymyxin-Induced Cell Death of Human Macrophage-Like THP-1 and Neutrophil-Like HL-60 Cells Associated with the Activation of Apoptotic Pathways

Author:

Fathalla Ahmed M.1,Chow Seong H.2,Naderer Thomas2,Zhou Qi Tony3,Velkov Tony4,Azad Mohammad A. K.1,Li Jian1ORCID

Affiliation:

1. Biomedicine Discovery Institute, Infection and Immunity Program and Department of Microbiology, Monash University, Clayton, Victoria, Australia

2. Biomedicine Discovery Institute, Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia

3. Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, Indiana, USA

4. Department of Pharmacology and Therapeutics, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, Victoria, Australia

Abstract

Innate immunity is crucial for the host to defend against infections, and understanding the effect of polymyxins on innate immunity is important for optimizing their clinical use. In this study, we investigated the potential toxicity of polymyxins on human macrophage-like THP-1 and neutrophil-like HL-60 cells. Differentiated THP-1 human macrophages (THP-1-dMs) and HL-60 human neutrophils (HL-60-dNs) were employed. Flow cytometry was used to measure the concentration-dependent effects (100 to 2,500 μM for THP-1-dMs and 5 to 2,500 μM for HL-60-dNs) and time-dependent effects (1,000 μM for THP-1-dMs and 300 μM for HL-60-dNs) of polymyxin B over 24 h.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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