title: Paracrine and juxtacrine lymphocyte enhancement of adherent macrophage and foreign body giant cell activation.
abstract: Lymphocytes have been shown to be involved in modulating monocyte and macrophage behavior in the foreign body reaction. Lymphocyte effects on biomaterial-adherent macrophage and foreign body giant cell (FBGC) behavior were further investigated by culturing monocytes alone or together with lymphocytes, either in direct co-cultures or indirectly in transwells, on a series of polyethylene terephthalate-based photograft co-polymerized material surfaces displaying distinct hydrophobic, hydrophilic/neutral, hydrophilic/anionic, and hydrophilic/ cationic chemistries. After periods of 3, 7, and 10 days, cytokine production was quantified by enzyme-linked immunosorbent assay and normalized to adherent macrophage/FBGC density to yield a measure of adherent macrophage/FBGC activation. Interactions with lymphocytes enhanced adherent macrophage and FBGC production of pro-inflammatory IL-1beta, TNF-alpha, IL-6, IL-8, and MIP-1beta on the hydrophobic and hydrophilic/cationic surfaces but had no effect on anti-inflammatory IL-10 production indicating lymphocytes promote a pro-inflammatory response to biomaterials. Lymphocytes also did not significantly influence MMP-9, TIMP-1, and TIMP-2 production. Interactions through indirect (paracrine) signaling showed a significant effect in enhancing adherent macrophage/FBGC activation at early time points whereas interactions via direct (juxtacrine) mechanisms dominated at later time points. Biomaterial surface chemistries differentially affected the observed responses as hydrophilic/neutral and hydrophilic/anionic surfaces, evoked the highest levels of activation relative to the other surfaces but did not facilitate lymphocyte enhancement of adherent macrophage/FBGC activation.
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: James M
authors.initials: JM
authors.lastname: Anderson
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000378:metabolism; D002448:Cell Adhesion; D016207:Cytokines / Q000096:biosynthesis; D015743:Giant Cells, Foreign-Body / Q000166:cytology* / Q000201:enzymology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology* / Q000201:enzymology; D020782:Matrix Metalloproteinases / Q000378:metabolism; D019899:Paracrine Communication; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases