Cationic liposomes evoke proinflammatory mediator release and neutrophil extracellular traps (NETs) toward human neutrophils.
Cationic liposomes are widely used as nanocarriers for therapeutic and diagnostic purposes. The cationic components of liposomes can induce inflammatory responses. This study examined the effect of cationic liposomes on human neutrophil activation. Cetyltrimethylammonium bromide (CTAB) or soyaethyl morpholinium ethosulfate (SME) was incorporated into liposomes as the cationic additive. The liposomes' cytotoxicity and their induction of proinflammatory mediators, intracellular calcium, and neutrophil extracellular traps (NETs) were investigated. The interaction of the liposomes with the plasma membrane triggered the stimulation of neutrophils. CTAB liposomes induced complete leakage of lactate dehydrogenase (LDH) at all concentrations tested, whereas SME liposomes released LDH in a concentration-dependent manner. CTAB liposomes proved to more effectively activate neutrophils compared with SME liposomes, as indicated by increased superoxide anion and elastase levels. Calcium influx increased 9-fold after treatment with CTAB liposomes. This influx was not changed by SME liposomes compared with the untreated control. Scanning electron microscopy (SEM) and immunofluorescence images indicated the presence of NETs after treatment with cationic liposomes. NETs could be quickly formed, within minutes, after CTAB liposomal treatment. In contrast to this result, NET formation was slowly and gradually increased by SME liposomes, within 4h. Based on the data presented here, it is important to consider the toxicity of cationic liposomes during administration in the body. This is the first report providing evidence of NET production induced by cationic liposomes.
Cell Pharmacology Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan, Taiwan; Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Kweishan, Taoyuan, Taiwan.
Tsong-Long
TL
Hwang
Department of Nutrition and Health Sciences, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan; Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan.
Ching-Yun
CY
Hsu
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Ibrahim A
IA
Aljuffali
Division of General Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan.
Chun-Han
CH
Chen
Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan, Taiwan.
Yuan-Ting
YT
Chang
Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan, Taiwan; Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan. Electronic address: fajy@mail.cgu.edu.tw.
Jia-You
JY
Fang
D000328:Adult; D002118:Calcium / Q000378:metabolism; D000077286:Cetrimonium; D002593:Cetrimonium Compounds / Q000737:chemistry*; D065206:Extracellular Traps / Q000187:drug effects; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D019272:Leukocyte Elastase / Q000378:metabolism*; D008081:Liposomes / Q000737:chemistry / Q000494:pharmacology*; D009025:Morpholines / Q000737:chemistry*; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D061251:Primary Cell Culture; D013481:Superoxides / Q000378:metabolism
D002593:Cetrimonium Compounds; D008081:Liposomes; D009025:Morpholines; D013481:Superoxides; C456974:cetethyl morpholinium; D007770:L-Lactate Dehydrogenase; D019272:Leukocyte Elastase; D002118:Calcium; D000077286:Cetrimonium
Cationic liposomes; Cytotoxicity; Inflammation; Neutrophil; Neutrophil extracellular traps