title: Inflammatory mimetic microfluidic chip by immobilization of cell adhesion molecules for T cell adhesion.
abstract: Leukocyte adhesion to adhesion molecules on endothelial cells is important in immune function, cancer metastasis and inflammation. This cell-cell binding is mediated via cell adhesion molecules such as E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) found on endothelial cells. Because these adhesion molecules on endothelial cells vary significantly across several disease conditions such as autoimmune diseases, inflammation or cancer metastasis, investigations of therapeutic agents that down-regulate leukocyte-endothelial interactions have been based on in vitro models using endothelial cell lines. Here we report a new model, an inflammatory mimetic microfluidic chip, which emulates leukocyte binding to cell adhesion molecules (CAM) by controlling the types and ratio of adhesion molecules. In our model, E-selectin was essential for the synergic binding of Jurkat T cells. Immunosuppressive drugs, such as tacrolimus (FK506) and cyclosporine A (CsA), were used to inhibit T cell interactions under the physiologic model of T cell migration at a ratio of 5 : 4.3 : 3.9 (E-selectin : ICAM-1 : VCAM-1). Our results support the potential usefulness of the inflammatory mimetic microfluidic chip as a T cell adhesion assay tool with modified adhesion molecules for applications such as immunosuppressive drug screening. The inflammatory mimetic microfluidic chip can also be used as a biosensor in clinical diagnostics, drug efficacy tests and high throughput drug screening due to the dynamic monitoring capability of the microfluidic chip.
authors: Department of Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, Korea.
authors: Sung Kyu
authors: SK
authors: Kim
authors: Won Kang
authors: WK
authors: Moon
authors: Joo Young
authors: JY
authors: Park
authors: Hyungil
authors: H
authors: Jung
mesh_terms: D032701:Biomimetics; D002448:Cell Adhesion / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D019040:E-Selectin / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D055767:Immobilized Proteins / Q000737:chemistry / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry / Q000378:metabolism*; D019169:Jurkat Cells; D046210:Microfluidic Analytical Techniques; D011485:Protein Binding; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D016559:Tacrolimus / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000737:chemistry / Q000378:metabolism*
chemical_list: D019040:E-Selectin; D055767:Immobilized Proteins; D007166:Immunosuppressive Agents; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D016572:Cyclosporine; D016559:Tacrolimus