title: C-reactive protein specifically enhances platelet-activating factor-induced inflammatory activity in vivo.
abstract: Platelet-activating factor (PAF) is a potent lipid mediator that is implicated in numerous inflammatory diseases. C-reactive protein (CRP) is an acute-phase plasma protein that increases rapidly and dramatically in response to inflammation. In this study, we investigated the effect of the interaction between CRP and PAF on inflammatory responses in vivo. From binding analysis using a time-resolved fluorometric assay, CRP bound to PAF and its precursor/metabolite lyso-PAF in a concentration-dependent manner. In addition, CRP bound to several phospholipids containing lysophosphatidylcholine, which bears structural resemblance to PAF and lyso-PAF, sphingosylphosphorylcholine, and lysophosphatidylethanolamine more readily than to lysophosphatidic acid and lysophosphatidylserine. In in vivo experiments using a rat model of hind paw oedema, CRP increased PAF-induced rat paw oedema in a dose-dependent manner, without causing the oedema itself, but it did not increase histamine and serotonin-induced paw oedema. Furthermore, the receptor for CRP, lectin-like oxidized low-density lipoprotein receptor 1 was not involved in the increase in PAF-induced inflammatory responses caused by CRP. These results indicate that CRP can specifically enhance PAF-induced inflammatory activity through binding to PAF and lyso-PAF. Therefore, CRP may accelerate the pathogenesis of numerous inflammatory diseases caused by PAF.
authors.affiliation: Faculty of Pharmacy, Iwaki Meisei University, 5-5-1, Chuodai-Iino, Iwaki, Fukushima 970-8551, Japan. Electronic address: a-sato@iwakimu.ac.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Sato
authors.affiliation: Faculty of Pharmacy, Iwaki Meisei University, 5-5-1, Chuodai-Iino, Iwaki, Fukushima 970-8551, Japan.
authors.forename: Keitaro
authors.initials: K
authors.lastname: Oe
authors.affiliation: Faculty of Pharmacy, Iwaki Meisei University, 5-5-1, Chuodai-Iino, Iwaki, Fukushima 970-8551, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Yamanaka
authors.affiliation: Faculty of Pharmacy, Iwaki Meisei University, 5-5-1, Chuodai-Iino, Iwaki, Fukushima 970-8551, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Yokoyama
authors.affiliation: Faculty of Pharmacy, Iwaki Meisei University, 5-5-1, Chuodai-Iino, Iwaki, Fukushima 970-8551, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ebina
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000008:administration & dosage / Q000502:physiology*; D004195:Disease Models, Animal; D004487:Edema / Q000209:etiology / Q000503:physiopathology; D006632:Histamine / Q000008:administration & dosage / Q000502:physiology; D018836:Inflammation Mediators / Q000008:administration & dosage / Q000502:physiology*; D008297:Male; D010743:Phospholipids / Q000378:metabolism; D010972:Platelet Activating Factor / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000502:physiology*; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000037:antagonists & inhibitors / Q000502:physiology; D012701:Serotonin / Q000008:administration & dosage / Q000502:physiology
chemical_list: D018836:Inflammation Mediators; C029271:O-deacetyl platelet activating factor; C495136:OLR1 protein, rat; D010743:Phospholipids; D010972:Platelet Activating Factor; D011994:Recombinant Proteins; D051127:Scavenger Receptors, Class E; D012701:Serotonin; D006632:Histamine; D002097:C-Reactive Protein
keywords: C-reactive protein; Inflammation; Inflammatory disease; Oedema; Platelet-activating factor