title: Fucoidan Stimulates Monocyte Migration via ERK/p38 Signaling Pathways and MMP9 Secretion.
abstract: Critical limb ischemia (CLI) induces the secretion of paracrine signals, leading to monocyte recruitment and thereby contributing to the initiation of angiogenesis and tissue healing. We have previously demonstrated that fucoidan, an antithrombotic polysaccharide, promotes the formation of new blood vessels in a mouse model of hindlimb ischemia. We examined the effect of fucoidan on the capacity of peripheral blood monocytes to adhere and migrate. Monocytes negatively isolated with magnetic beads from peripheral blood of healthy donors were treated with fucoidan. Fucoidan induced a 1.5-fold increase in monocyte adhesion to gelatin (p < 0.05) and a five-fold increase in chemotaxis in Boyden chambers (p < 0.05). Fucoidan also enhanced migration 2.5-fold in a transmigration assay (p < 0.05). MMP9 activity in monocyte supernatants was significantly enhanced by fucoidan (p < 0.05). Finally, Western blot analysis of fucoidan-treated monocytes showed upregulation of ERK/p38 phosphorylation. Inhibition of ERK/p38 phosphorylation abrogated fucoidan enhancement of migration (p < 0.01). Fucoidan displays striking biological effects, notably promoting monocyte adhesion and migration. These effects involve the ERK and p38 pathways, and increased MMP9 activity. Fucoidan could improve critical limb ischemia by promoting monocyte recruitment.
authors.affiliation: Inserm UMR_S 1140, Faculté de Pharmacie, Université Paris Descartes, Sorbonne Paris Cité, 4 Avenue de l'observatoire Paris 75006, France. elene.sapharikas@parisdescartes.fr.
authors.forename: Elene
authors.initials: E
authors.lastname: Sapharikas
authors.affiliation: Inserm UMR_S 1140, Faculté de Pharmacie, Université Paris Descartes, Sorbonne Paris Cité, 4 Avenue de l'observatoire Paris 75006, France. anna.lokajczyk@parisdescartes.fr.
authors.forename: Anna
authors.initials: A
authors.lastname: Lokajczyk
authors.affiliation: Inserm UMR-S 970, AP-HP, Hôpital Européen Georges Pompidou, 20 rue Leblanc Paris 75015, France. anne-marie.fischer@egp.aphp.fr.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Fischer
authors.affiliation: Inserm UMR_S 1140, Faculté de Pharmacie, Université Paris Descartes, Sorbonne Paris Cité, 4 Avenue de l'observatoire Paris 75006, France. catherine.boisson-vidal@parisdescartes.fr.
authors.forename: Catherine
authors.initials: C
authors.lastname: Boisson-Vidal
mesh_terms: D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D016023:Integrins / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism* / Q000502:physiology; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D011134:Polysaccharides / Q000494:pharmacology*; D054390:Receptors, CCR2 / Q000502:physiology
chemical_list: D016023:Integrins; D011134:Polysaccharides; D054390:Receptors, CCR2; C007789:fucoidan; D020780:Matrix Metalloproteinase 9
keywords: critical limb ischemia; fucoidan; migration; monocytes