Fucoidan Stimulates Monocyte Migration via ERK/p38 Signaling Pathways and MMP9 Secretion

• Published in: Marine drugs Vol. 13; no. 7; pp. 4156 - 4170
• Main Authors: Sapharikas, Elene, Lokajczyk, Anna, Fischer, Anne-Marie, Boisson-Vidal, Catherine
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 30.06.2015; MDPI
• Subjects: Adhesion; Biological effects; Blotting, Western; Cell Adhesion - drug effects; Cell Movement - drug effects; Cellular Biology; critical limb ischemia; Dose-Response Relationship, Drug; Flow Cytometry; fucoidan; Humans; Integrins - physiology; Life Sciences; MAP Kinase Signaling System - drug effects; MAP Kinase Signaling System - physiology; Matrix Metalloproteinase 9 - physiology; Matrix Metalloproteinase 9 - secretion; migration; monocytes; Monocytes - drug effects; Monocytes - physiology; Polysaccharides - pharmacology; Receptors, CCR2 - physiology; migration; monocytes; critical limb ischemia; fucoidan
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md13074156

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.