Diffusion and reactions of nitric oxide, oxygen, and superoxide in cells and culture media

As part of the non-specific immune response to infection, activated macrophages synthesize nitric oxide (NO) at relatively high rates, thereby creating local concentrations of NO that are toxic to the invading microorganisms. However, high rates of NO synthesis can also damage host tissues, especially if prolonged (as in chronic inflammations). Although NO can act directly, much of its cytotoxicity and genotoxicity may be due to peroxynitrite (ONOO-), formed by the rapid reaction of NO with superoxide (02-)- Superoxide is a byproduct of mitochondrial respiration and of certain cytosolic reactions, and it is present in virtually all cells. Thus, intracellular ONOO- formation is inevitable when cells are exposed to NO, which diffuses readily across cell membranes. Superoxide is generated also by an NADPH oxidase on the external membrane surface of macrophages, thereby delivering it to the extracellular fluid at significant rates. The research in this thesis aimed to determine the concentration profiles of NO and related species in cell cultures and tissues. Toward that end, the diffusion and reactions of NO, 02, and 02- were studied by mathematical modeling and by experimental work with macrophage cultures. The results obtained will be useful in designing NO toxicity experiments and in determining potentially toxic conditions in body tissues. A mathematical model was developed to predict the intracellular concentrations of NO, 02-, and ONOO- in suspension cell cultures exposed to NO and/or peroxynitrite. Steady-state concentrations were computed as a function of radial position within an idealized spherical cell, with a distinction being made between cytosolic and mitochondrial values.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemical Engineering.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2004

Author dc:creator

• Nalwaya, Nitesh, 1979-

Advisor dc:contributor.advisor

• William M. Deen.

• Chemical Engineering.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/29376

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/29376