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
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.