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Debra L. Laskin
Professor II and Chair
Rutgers University
Department of Pharmacology & Toxicology
Roy A. Bowers Endowed Chair
Ernest Mario School of Pharmacy
Busch Campus
Piscataway. NJ 08854
(732) 445-5862
FAX - 2534
laskin@eohsi.rutgers.edu |
Immunology. macrophages. nitric oxide. inflammation
The overall focus of the
research in my laboratory is immunology. We are particularly interested in
nonspecific immunity mediated by macrophages. which are critical cellular
components of the host response to tissue injury. Although the involvement of
macrophages in protecting against invading pathogens and tumor cells is well
documented. recent studies from our laboratory have demonstrated that
macrophages also have a dark side. Thus they can be activated to release
excessive quantities of proinflammatory and cytotoxic mediators that actually
promote tissue injury. An analysis of this process represents the main focus of
our research. Two mouse models are being utilized to investigate the role of
macrophages and inflammatory mediators in toxicity: the lung and the liver. In
each of these tissues. we found that exposure of mice to xenobiotics is
associated with localized accumulation of macrophages. Moreover. macrophages
isolated from the lung or liver of animals treated with tissue specific
toxicants such as ethanol. acetaminophen. or ozone are "activated" to release
increased quantities of inflammatory mediators such as tumor necrosis factor
alpha. nitric oxide and superoxide anion. To analyze the role of these
cytotoxic mediators in toxicity. both pharmacologic inhibitors and knockout mice
are being utilized. Whereas in some model systems. both approaches result in
similar results in others such as hepatic necrosis induced by acetaminophen
administration. opposing results are obtained. Thus. in this model. anti-TNFα
antibody prevents toxicity. while TNFα knockout mice were more sensitive to
acetaminophen. These data suggest that there are limitations to the use of
transgenic animals which may be related to compensatory alterations in cytotoxic
mediators production and this is being investigated. Another aspect of our
studies is to elucidate biochemical mechanisms mediating macrophage activation
in the liver and the lung. This has involved investigations on signaling
molecules such as MAP kinases. and transcription factors such as NFkB. C/EBP and
AP-1. Much of our research has taken advantage of new technological
developments in biochemistry. molecular biology and flow cytometry/image
analysis.
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