title: The effect of cyclic mechanical strain on activation of dendritic cells cultured on adhesive substrates.
abstract: Dendritic cells (DCs), key regulators of tolerance and immunity, have been found to reside in mechanically active tissues such as the interior layers of the arterial wall, which experience cyclic radial wall strain due to pulsatile blood flow. Although experimentally difficult to determine in vivo, it is reasonable to postulate DCs experience the mechanical forces in such mechanically active tissues. However, it is currently unknown how DCs respond to cyclic mechanical strain. In order to explore the hypothesis that DCs are responsive to mechanical strain, DCs were cultured in vitro on pre-adsorbed adhesive proteins (e.g., laminin, collagen, fibrinogen) and 1 Hz cyclic strain was applied for various durations and strain magnitudes. It was determined that a strain magnitude of 10% and 24 h duration adversely affected DC viability compared to no-strain controls, but culture on certain adhesive substrates provided modest protection of viability under this harsh strain regime. In contrast, application of 1 h of 1 Hz cyclic 3% strain did not affect DC viability and this strain regime was used for the remaining experiments for quantifying DC activation and T-cell priming capability. Application of 3% strain increased expression of stimulatory (MHC-II) and costimulatory molecules (CD86, CD40), and this effect was generally increased by culture on pre-coated adhesive substrates. Interestingly, the cytokine secretion profile of DCs was not significantly affected by strain. Lastly, strained DCs demonstrated increased stimulation of allogeneic T-cell proliferation, in a manner that was independent of the adhesive substrate. These observations indicate generation of a DC consistent with what has been described as a semi-mature phenotype. This work begins elucidating a potential role for DCs in tissue environments exposed to cyclic mechanical forces.
authors.affiliation: J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Jamal S
authors.initials: JS
authors.lastname: Lewis
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Dolgova
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Chancellor
authors.forename: Abhinav P
authors.initials: AP
authors.lastname: Acharya
authors.forename: Jerome V
authors.initials: JV
authors.lastname: Karpiak
authors.forename: Tanmay P
authors.initials: TP
authors.lastname: Lele
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Keselowsky
mesh_terms: D000269:Adhesives / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005353:Fibronectins / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013314:Stress, Mechanical; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D019096:Vitronectin / Q000494:pharmacology
chemical_list: D000269:Adhesives; D016207:Cytokines; D005353:Fibronectins; D019096:Vitronectin; D012710:Serum Albumin, Bovine
keywords: Cell adhesion; Dendritic cells; Extracellular matrix; Immunology; Mechanical force; Mechanical strain