Low-dose sulfur mustard primes oxidative function and induces apoptosis in human polymorphonuclear leukocytes.
Although considerable work has focused on understanding the processes of direct tissue injury mediated by the chemical warfare vesicant, sulfur mustard (2,2'-bis-chloroethyl sulfide; SM), relatively little is known regarding the mechanisms of secondary injury caused potentially by the acute inflammatory response that follows SM exposure. Polymorphonuclear leukocytes (PMNs) play a central role in the initiation and propagation of inflammatory responses that, in some cases, result in autoimmune tissue damage. The potential for PMN-derived tissue damage following SM exposure may, in part, account for the protracted progression of the injury before it resolves. The current study was undertaken to evaluate the priming, oxidative function, and viability of PMN following exposure to low doses of SM such as those that might remain in tissues as a result of topical exposure. Our results demonstrate that doses of SM ranging from 25 to 100 microM primed PMN for oxidative burst in response to activation by fMLP, and that doses of SM ranging from 50 to 100 microM induced PMN apoptosis. Understanding the mechanisms through which SM directly affects PMN activation and apoptosis will be of critical value in developing novel treatments for inflammatory tissue injury following SM exposure.
Levitt
Jonathan M
JM
Michael E. DeBakey Department of Surgery, Baylor College of Medicine, 6550 Fannin, Houston, TX 77030, USA.
Lodhi
Irfan J
IJ
Nguyen
Phu Kim
PK
Ngo
Vinh
V
Clift
Russell
R
Hinshaw
Daniel B
DB
Sweeney
John F
JF
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D005453:Fluorescence; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D009151:Mustard Gas / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism*; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D017452:Receptors, IgG / Q000096:biosynthesis / Q000235:genetics; D013268:Stimulation, Chemical; D014466:Ultraviolet Rays
D007202:Indicators and Reagents; D016877:Oxidants; D017382:Reactive Oxygen Species; D017452:Receptors, IgG; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D009151:Mustard Gas