Diversity of endotoxin-induced nitrotyrosine formation in macrophage-endothelium-rich organs.
The administration of bacterial lipopolysaccharide (LPS; endotoxin) can stimulate the development of the systemic inflammatory response syndrome, which can compromise the function of many organ systems, resulting in multiple organ failure. Activation of macrophages and cytokines by endotoxin and the subsequent formation of reactive oxygen and nitrogen species are of central pathogenic importance in various inflammatory diseases including sepsis. However, whether different tissues behave the same in pathological changes produced by LPS and what factors may affect pathological processes and protein tyrosine nitration in different organs, still remain to be evaluated. In the present study, we investigated the distribution of nitrotyrosine and other pathological changes induced by LPS in rat liver, spleen, and lung, all of which are rich in macrophages and endothelial cells. Our study revealed two important findings: first, a denitration activity in spleen white pulp might play a key role to protect the areas from nitration. Similar activity might also exist in endothelial cells of sinusoids and capillaries. Second, protein nitration might not induce significant tissue damage as shown in liver and spleen. However, inflammatory infiltration with increased formation NO* and other reactive species may result in severe tissue injury, as demonstrated in lung after LPS administration.
Bian
K
K
Department of Integrative Biology, Physiology, and Pharmacology, and the Institute of Molecular Medicine, The University of Texas-Houston Medical School, Houston, TX 77030, USA.
Murad
F
F
D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism*; D015151:Immunoblotting; D007124:Immunoenzyme Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D013481:Superoxides / Q000494:pharmacology*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism*
D008070:Lipopolysaccharides; D009419:Nerve Tissue Proteins; D013481:Superoxides; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; C002385:linsidomine; D008981:Molsidomine; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496322:Nos1 protein, rat; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat