title: A three-dimensional in vitro model to demonstrate the haptotactic effect of monocyte chemoattractant protein-1 on atherosclerosis-associated monocyte migration.
abstract: Monocyte transendothelial migration is a multi-step process critical for the initiation and development of atherosclerosis. The chemokine monocyte chemoattractant protein-1 (MCP-1) is overexpressed during atheroma and its concentration gradients in the extracellular matrix (ECM) is critical for the transendothelial recruitment of monocytes. Based on prior observations, we hypothesize that both free and bound gradients of MCP-1 within the ECM are involved in directing monocyte migration. The interaction between a three-dimensional (3D), cell-free, collagen matrix and MCP-1; and its effect on monocyte migration was measured in this study. Our results showed such an interaction existed between MCP-1 and collagen, as 26% of the total MCP-1 added to the collagen matrix was bound to the matrix after extensive washes. We also characterized the collagen-MCP-1 interaction using biophysical techniques. The treatment of the collagen matrix with MCP-1 lead to increased monocyte migration, and this phenotype was abrogated by treating the matrix with an anti-MCP-1 antibody. Thus, our results indicate a binding interaction between MCP-1 and the collagen matrix, which could elicit a haptotactic effect on monocyte migration. A better understanding of such mechanisms controlling monocyte migration will help identify target cytokines and lead to the development of better anti-inflammatory therapeutic strategies.
authors.affiliation: School of Chemical Engineering at Oklahoma State University, Stillwater, OK, 74078, USA.
authors.forename: Neda
authors.initials: N
authors.lastname: Ghousifam
authors.affiliation: Department of Chemistry at Oklahoma State University, Stillwater, OK, 74078, USA.
authors.forename: Hamid
authors.initials: H
authors.lastname: Mortazavian
authors.affiliation: School of Chemical Engineering at Oklahoma State University, Stillwater, OK, 74078, USA.
authors.forename: Rudra
authors.initials: R
authors.lastname: Bhowmick
authors.affiliation: Department of Chemistry at Oklahoma State University, Stillwater, OK, 74078, USA.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Vasquez
authors.affiliation: Department of Chemistry at Oklahoma State University, Stillwater, OK, 74078, USA.
authors.forename: Frank D
authors.initials: FD
authors.lastname: Blum
authors.affiliation: School of Chemical Engineering at Oklahoma State University, Stillwater, OK, 74078, USA. Electronic address: heather.fahlenkamp@okstate.edu.
authors.forename: Heather
authors.initials: H
authors.lastname: Gappa-Fahlenkamp
mesh_terms: D002448:Cell Adhesion; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009000:Monocytes / Q000473:pathology*; D058226:Plaque, Atherosclerotic / Q000378:metabolism* / Q000473:pathology*; D013696:Temperature
chemical_list: D018932:Chemokine CCL2; D003094:Collagen
keywords: Atherosclerosis; Monocyte chemoattractant protein-1; Monocyte migration