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Reactive oxygen and nitrogen species in leukocyte adhesion and transmigration: a computational model
Author(s) -
Lakshmanan Nisha,
Kavdia Mahendra
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.1007.6
Subject(s) - peroxynitrite , superoxide , nitric oxide , adhesion , chemistry , nitrotyrosine , peroxynitrous acid , biophysics , cell adhesion molecule , microbiology and biotechnology , reactive nitrogen species , endothelium , cell adhesion , reactive oxygen species , biochemistry , immunology , nitric oxide synthase , biology , enzyme , endocrinology , organic chemistry
In hyperglycemia, there is a significant increase in the levels of tyrosine nitration causing an increase in circulating adhesion molecules. This leads to a greater number of leukocytes that roll and adhere on the vascular endothelium resulting in endothelial cell dysfunction. Some of the adhered leukocytes also cross the endothelial junction barrier and migrate from the lumen to the surrounding spaces. Inducible nitric oxide synthase in these leukocytes produces nitric oxide and superoxide, thereby producing more of peroxynitrite and nitrotyrosine. To better understand this vicious cycle, we formulated a mathematical model of a tissue containing a blood vessel and simulated varying degrees of leukocyte adhesion and transmigration. The model predicts an increase in the peak levels of nitric oxide, superoxide and peroxynitrite at and around the site of adhesion; from 83, 2 and 3.5 nM respectively, in the case of no adhesion to 104, 13.5 and 35 nM when leukocytes adhere. However, the extent of transport is a few microns for superoxide to 10's of microns for peroxynitrite. Results indicate that peroxynitrite can cause tissue injury over a wide area across the adhesion site and trigger further leukocyte adhesion. The model helps elucidate some important aspects of complex leukocyte‐endothelium interactions such as signaling, injury and adhesive response. Supported by: AHA 0530050N and NIH R01 HL084337 & R15 HL087287.