Depletion of antigen-presenting cells by clodronate liposomes reverses the psoriatic skin phenotype in KC-Tie2 mice.

BACKGROUND: There is ongoing debate regarding the initiation of psoriatic plaque as primarily arising from an anomaly in epidermal keratinocytes (KCs) or from abnormalities in immunocytes that secondarily activate otherwise normal KCs. In mice engineered to overexpress the angiopoietin receptor Tie2 in KCs, skin spontaneously develops the characteristic clinical, histological and immune cell phenotypes of psoriasis which can be reversed with either transgene repression or ciclosporin administration, suggesting key roles for both KCs and T cells in mediating the skin disease in this murine model. OBJECTIVES: To determine if antigen-presenting cells (APCs) and macrophages alone are sufficient to sustain psoriasiform inflammation in the KC-Tie2 murine model of psoriasis. METHODS: Clodronate liposomes were intradermally injected into involved dorsal skin of KC-Tie2 or control animals once a week for 6weeks and acanthosis, angiogenesis, immune cell infiltration and cytokine production were quantitated using immunohistochemistry and interactive image analyses, enzyme-linked immunosorbent assay (ELISAs) and quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Clodronate liposome injection eliminated CD11c+, F4/80+ and CD11b+ cells in the skin and returned CD8+ T-cell numbers to control mouse levels. APC depletion in KC-Tie2 mouse skin resulted in resolution of the acanthotic skin phenotype, decreased dermal angiogenesis, and a return to control mouse levels for interleukin (IL)-1α, IL-6, IL-23 and tumour necrosis factor (TNF)-α expression and modest reductions in interferon-γ and IL-17. CONCLUSIONS: These findings suggest a critical role for APCs and myeloid cell-derived IL-23 and TNF-α and underscore the importance of Th1 and Th17 T cells in maintaining the psoriasiform skin phenotype in the KC-Tie2 mouse model.

Short-term plasma-cleaning treatments enhance in vitro osteoblast attachment to titanium.

The purpose of this research was to characterize the in vitro cellular behavior of osteoblast-like cells on titanium surfaces prepared with argon plasma-cleaning (PC) treatments for various lengths of time. The highest levels of cell attachment were observed for surfaces which had been plasma-treated for one min. Surface analyses indicated that although PC treatments dramatically improved surface wettability, the presence of inorganic contaminants was observed with longer treatment times and may have interfered with cell attachment. Further work is suggested to investigate the longer-term phenotypic expression of osteoblasts when grown on implant surfaces.

Optimization of surface micromorphology for enhanced osteoblast responses in vitro.

In vitro cellular responses of osteoblast-like cells were studied on titanium surfaces with different surface morphologies. Surface profilometry was used to determine whether rough or smooth surfaces with regular or irregular morphologies can be produced by conventional fabrication techniques. Significantly higher levels of cellular attachment were found using rough, sandblasted surfaces with irregular morphologies. These results correlate with recent in vivo findings and suggest that implants should be prepared with roughened surfaces at bony contact areas.

In vitro periodontal ligament fibroblast attachment to plasma-cleaned titanium surfaces.

The objective of this research was to characterize the in vitro cellular behavior of fibroblast-like cells derived from rat periodontal ligament on commercially pure titanium surfaces which were sterilized by a variety of treatments. Following standard surface preparation protocols, the Ti specimens were sterilized by either steam autoclaving, exposure to ethylene oxide gas, exposure to ultraviolet light, or plasma-cleaning in argon for either one min or five min. Fibroblast-like cells in serum-supplemented media were incubated on the various Ti specimens for up to two h. In general, the levels of cell attachment for plasma-cleaned surfaces were significantly higher than those for steam-sterilized surfaces, but were significantly lower than the attachment levels for both the ultraviolet-treated surfaces and the tissue culture plastic control. The duration of plasma cleaning itself did not have a significant effect on the percentage of cell attachment at any time period. SEM evaluations indicated that by two h, the cellular morphology was different on the variously treated specimens. These studies indicate that the method of sterilization following implant surface preparation can affect the initial in vitro biological events of cell attachment and spreading.