title: Lymphocyte adhesion and interactions with biomaterial adherent macrophages and foreign body giant cells.
abstract: To characterize the effects of adherent macrophages and biomaterial surface chemistries on lymphocyte adhesion and activation, lymphocytes were co-cultured with monocytes alone and together, directly and separated by a porous membrane transwell on hydrophobic, hydrophilic/neutral, hydrophilic/anionic, and hydrophilic/cationic biomaterial surfaces. Surface adherent cells were quantitatively analyzed after 3 days utilizing immunofluorescence and phase contrast imaging. After periods of 3, 7, and 10 days, secreted interferon-gamma (IFN-gamma) was quantified by ELISA. Limited direct biomaterial-adherent lymphocytes were identified regardless of the presence of macrophages or foreign body giant cells (FBGC). The majority of adherent lymphocytes, which were T cells (>95%) rather than natural killer cells, predominantly interacted with adherent macrophages and FBGCs; greater than 90% were interacting on surfaces with higher levels of adherent macrophages and FBGCs and greater than 55% were interacting on surfaces with lower levels of macrophages and FBGCs. The hydrophilic/anionic surface promoted higher levels of macrophage- and FBGC-adherent lymphocytes but was nonselective for lymphocyte subtype interactions. The hydrophilic/neutral surface was selective for CD4+ T lymphocyte interactions while the hydrophobic surface was selective for CD8+ T lymphocyte interactions. IFN-gamma was produced in direct and indirect co-cultures but not in lymphocyte- and monocyte-only cultures suggesting that lymphocytes are activated via macrophage-derived cytokines rather than direct biomaterial contact. Direct lymphocyte interactions with adherent macrophages/FBGCs enhanced IFN-gamma production relative to indirect co-cultures. These results suggest that lymphocytes prefer interactions with adherent macrophages and FBGCs, resulting in lymphocyte activation, and these interactions can be influenced by biomaterial surface chemistries.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: David T
authors.initials: DT
authors.lastname: Chang
authors.forename: Erica
authors.initials: E
authors.lastname: Colton
authors.forename: Takehisa
authors.initials: T
authors.lastname: Matsuda
authors.forename: James M
authors.initials: JM
authors.lastname: Anderson
mesh_terms: D001672:Biocompatible Materials / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects*; D005455:Fluorescent Antibody Technique; D015743:Giant Cells, Foreign-Body / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008222:Lymphokines / Q000096:biosynthesis; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D013499:Surface Properties / Q000187:drug effects
chemical_list: D001672:Biocompatible Materials; D008222:Lymphokines