title: Platelet activating factor is elevated in cerebral spinal fluid and plasma of patients with relapsing-remitting multiple sclerosis.
abstract: Platelet-activating factor (PAF) is a phospholipid mediator of inflammation with a wide range of biological activities, including the alteration of barrier function of endothelium. A biological assay combined with high pressure liquid chromatography-tandem mass spectrometry showed that plasma and cerebral spinal fluid (CSF) PAF levels in 20 patients with relapsing/remitting or secondary progressive multiple sclerosis (MS) studied by magnetic resonance imaging (MRI) were significantly higher than in healthy controls (plasma: 3.29+/-4.52 vs. 0.48+/-0.36 ng/ml, p < 0.002; CSF: 4.95+/-6.22 ng/ml vs. 0.01+/-0.04 ng/ml, p < 0.0001). Values were also significantly higher in relapsing/remitting than in secondary progressive (plasma: 5.10+/-4.97 vs. 0.52+/-0.85 ng/ml, p < 0.005; CSF: 8.59+/-6.39 vs. 0.55+/-0.68 ng/ml, p < 0.002). It was also found that both plasma (R2: 0.65) and CSF (R2:0.72) levels were correlated with the MRI number of gadolinium enhancing lesions, which are markers of blood-brain barrier (BBB) injury, whereas their peaks were not correlated with the MRI number of white matter lesions, nor with the expanded disability status score (EDSS) according to Kurtze [Kurtze, J.F., 1983. Rating neurological impairment in multiple sclerosis: an expanded disability scale (EDSS). Neurology 33, 1444-1452]. Both plasma and CSF in patients with relapsing/remitting MS and marked gadolinium enhancement contained the two major molecular species of PAF: 1-0-hexadecyl- (C16:O) and 1-0-octadecyl-sn-glycero-3-phosphocholine (C18:O). The ratio of the two molecular species was different in the two biological fluids, being PAF C18:0 more abundant in CSF and PAF C16:0 in plasma, indicating a different cellular origin of PAF or different enzymatic processing. These findings suggest that PAF is a significant mediator of BBB injury in the early stages of MS, rather than a marker of its progression and severity.
authors.affiliation: Department of Neurology, Ospedale Rovato, Brescia, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Callea
authors.forename: M
authors.initials: M
authors.lastname: Arese
authors.forename: A
authors.initials: A
authors.lastname: Orlandini
authors.forename: C
authors.initials: C
authors.lastname: Bargnani
authors.forename: A
authors.initials: A
authors.lastname: Priori
authors.forename: F
authors.initials: F
authors.lastname: Bussolino
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000032:analysis / Q000134:cerebrospinal fluid*; D001812:Blood-Brain Barrier / Q000276:immunology*; D002196:Capillaries / Q000276:immunology / Q000378:metabolism; D002648:Child; D018450:Disease Progression; D005260:Female; D005682:Gadolinium; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D010972:Platelet Activating Factor / Q000031:analogs & derivatives* / Q000032:analysis / Q000134:cerebrospinal fluid / Q000235:genetics; D012008:Recurrence
chemical_list: D000959:Antihypertensive Agents; D010972:Platelet Activating Factor; C037145:1-hexadecyl-2-acetyl-glycero-3-phosphocholine; C026613:1-0-octadecyl 2-0-acetyl sn-glycero-3-phosphorylcholine; D005682:Gadolinium