Roles for platelet-activating factor and center dot NO-derived oxidants causing neutrophil adherence after CO poisoning

Citation
Sr. Thom et al., Roles for platelet-activating factor and center dot NO-derived oxidants causing neutrophil adherence after CO poisoning, AM J P-HEAR, 281(2), 2001, pp. H923-H930
Citations number
51
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
ISSN journal
03636135 → ACNP
Volume
281
Issue
2
Year of publication
2001
Pages
H923 - H930
Database
ISI
SICI code
0363-6135(200108)281:2<H923:RFPFAC>2.0.ZU;2-S
Abstract
Studies were conducted with rats to investigate whether platelet activating factor (PAF) and nitric oxide (. NO)-derived oxidants played roles in the initial adherence of neutrophils to vasculature in the brain after carbon m onoxide (CO) poisoning. Before CO poisoning, rats were treated with the com petitive PAF receptor antagonist WEB-2170 or with the peroxynitrite scaveng er selenomethionine. Both agents caused significantly lower concentrations of myeloperoxidase in the brain after poisoning, indicating fewer sequester ed neutrophils. Similarly, both agents reduced the concentration of nitroty rosine, indicating less oxidative stress due to . NO-derived oxidants. Ther e were no alterations in whole brain homogenate PAF concentration measured by immunoassay and bioassay, nor were there changes in phosphatidylcholine concentration. Immunohistochemical imaging showed PAF to be more heavily lo calized within perivascular zones after CO poisoning. Neutrophils colocaliz ed with both PAF and nitrotyrosine in brains of rats killed immediately aft er CO poisoning. We conclude that qualitative changes in brain PAF are resp onsible for neutrophil adherence immediately after CO poisoning and that ac tivated neutrophils trigger the initial rise in brain nitrotyrosine. Persis tent PAF-mediated neutrophil adherence required production of . NO-derived oxidants because when oxidants were scavenged, neutrophil adherence was not maintained.