Loss of stromal cell Thy-1 plays a critical role in lipopolysaccharide induced chronic lung allograft dysfunction.

BACKGROUND: Long-term survival of lung transplants lags behind other solid organs due to early onset of a fibrotic form of chronic rejection known as chronic lung allograft dysfunction (CLAD). Preventing CLAD is difficult as multiple immunologic and physiologic insults contribute to its development. Targeting fibroblast activation, which is the final common pathway leading to CLAD, offers the opportunity to ameliorate fibrosis irrespective of the initiating insult. Thy-1 is a surface glycoprotein that controls fibroblast differentiation and activation. METHODS: To study the role of Thy-1 in CLAD, we utilized the minor antigen mismatched C57BL/6 (B6wild-type) or B6Thy-1-/-→C57BL/10 (B10) model of murine orthotopic lung transplantation with postoperative bacterial infection modeled by intratracheal lipopolysaccharide (LPS) administration. The effects of LPS on Thy-1 expression, proliferation, and gene expression were assessed in fibroblasts in vitro and the therapeutic potential of Thy-1 replacement was assessed in vivo. RESULTS: More severe CLAD was evident in B6Thy-1-/- →B10 grafts compared to B6wild-type →B10 grafts. LPS further accentuated fibrosis in B6wild-type →B10 grafts with some, but limited, effects on B6Thy-1-/- →B10 grafts. LPS contributed to Thy-1 loss from Thy-1(+) fibroblasts in vitro due to a decrease in mRNA expression. In addition, LPS promoted proliferation and upregulation of multiple inflammatory pathways in Thy-1(-) fibroblasts by gene expression analysis. Most importantly, replacement of Thy-1 through exogenous administration ameliorated the fibrotic phenotype post-LPS mediated modeling of infection. CONCLUSIONS: Our findings suggest that the loss of Thy-1 on fibroblasts is a previously unrecognized cause of CLAD and its replacement may offer therapeutic applications for amelioration of this disease post-transplantation in the setting of infectious stress responses.

Effects of an external foci of attention at different distances on standing long jump in non-athletes.

[Purpose] External focus (EF) instructions demonstrate a learning effect on motor performance enhancement. However, the effective EF distance during standing long jump performance of non-athletes has not been clarified. This study aimed to determine the effects of EF at different distances on jumping performance. [Participants and Methods] A total of 40 non-athlete participants were randomly divided among four groups. The no attention line group performed a standing long jump without the attention line on the floor; those in the -20-cm EF group, the ± 0-cm EF group, and +20-cm EF group performed the jump attention line with an attention line 20-cm posterior, at ± 0 cm, and 20-cm anterior as the reference jump distances, respectively. [Results] The mean rate of increase between the first to second jump distances in the +20-cm EF group was higher than that in the no attention line group. The rates at which the jumpers reached the attention line in the ± 0-cm EF group and the +20-cm EF group were lower than the rate in the -20-cm EF group. [Conclusion] Instructions are more effective when the distance to the attention line exceeds jumping performance.