scholarly journals P.159: Investigating the Role of Cathepsin L in Islet Graft Rejection

2021 ◽  
Vol 105 (12S1) ◽  
pp. S66-S66
Author(s):  
KaLia Burnette ◽  
Samuel I. Blum
2010 ◽  
Vol 19 (5) ◽  
pp. 597-612 ◽  
Author(s):  
Preeti Chhabra ◽  
Kunjie Wang ◽  
Qiang Zeng ◽  
Mladen Jecmenica ◽  
Linda Langman ◽  
...  

2000 ◽  
Vol 69 (Supplement) ◽  
pp. S196
Author(s):  
Tao Wu ◽  
Zhiguang Guo ◽  
Alison M. Trexler ◽  
Nicole Kirchhof ◽  
Hideo Yagita ◽  
...  
Keyword(s):  

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Miao-Miao Zhao ◽  
Wei-Li Yang ◽  
Fang-Yuan Yang ◽  
Li Zhang ◽  
Wei-Jin Huang ◽  
...  

AbstractTo discover new drugs to combat COVID-19, an understanding of the molecular basis of SARS-CoV-2 infection is urgently needed. Here, for the first time, we report the crucial role of cathepsin L (CTSL) in patients with COVID-19. The circulating level of CTSL was elevated after SARS-CoV-2 infection and was positively correlated with disease course and severity. Correspondingly, SARS-CoV-2 pseudovirus infection increased CTSL expression in human cells in vitro and human ACE2 transgenic mice in vivo, while CTSL overexpression, in turn, enhanced pseudovirus infection in human cells. CTSL functionally cleaved the SARS-CoV-2 spike protein and enhanced virus entry, as evidenced by CTSL overexpression and knockdown in vitro and application of CTSL inhibitor drugs in vivo. Furthermore, amantadine, a licensed anti-influenza drug, significantly inhibited CTSL activity after SARS-CoV-2 pseudovirus infection and prevented infection both in vitro and in vivo. Therefore, CTSL is a promising target for new anti-COVID-19 drug development.


2021 ◽  
pp. 101415
Author(s):  
Isabella Hanka ◽  
Thomas Stamminger ◽  
Martina Ramsperger-Gleixner ◽  
V. Annika Kuckhahn ◽  
Regina Müller ◽  
...  

1998 ◽  
Vol 30 (2) ◽  
pp. 589 ◽  
Author(s):  
Z. Guo ◽  
D. Mital ◽  
Y-Y. Mo ◽  
Y. Tian ◽  
J. Shen ◽  
...  

2020 ◽  
Vol 22 (4) ◽  
Author(s):  
Gaetano Alfano ◽  
Giovanni Guaraldi ◽  
Francesco Fontana ◽  
Erica Franceschini ◽  
Giovanni Dolci ◽  
...  

1981 ◽  
Vol 196 (1) ◽  
pp. 41-48 ◽  
Author(s):  
S E Knowles ◽  
F J Ballard ◽  
G Livesey ◽  
K E Williams

1. The effects of leupeptin and other microbial proteinase inhibitors were measured in rat yolk sacs on the uptake and degradation of formaldehyde-denatured 125I-labelled bovine serum albumin as well as on the degradation of 3H-labelled endogenous protein. 2. Leupeptin, at concentrations between 1 and 100 micrograms/ml, inhibits the degradation of added albumin without affecting pinocytic uptake. Accordingly large amounts of undegraded albumin accumulate within the tissue. 3. Removal of leupeptin produces a rapid recovery of the capacity to degrade albumin. 4. Endogenous protein degradation is rapidly inhibited by leupeptin, but to a far lesser extent than the breakdown of albumin. However, the inhibition is only slightly reversed on removal of leupeptin. 5. Degradation of both albumin and endogenous protein in intact yolk sacs is inhibited by the microbial proteinase inhibitors in the order: leupeptin greater than antipain greater than chymostatin; elastatinal, pepstatin and bestatin are ineffective. 6. Similar results are found when albumin is incubated in yolk-sac homogenates at pH 4 with the inhibitors. 7. The marked inhibitory effects of leupeptin, antipain and chymostatin suggest that cathepsin B and possibly cathepsin L participate in the degradation of 125I-labelled albumin in yolk sacs. By comparison, the smaller inhibitory effects of the proteinase inhibitors on endogenous protein breakdown imply a minor role of lysosomal cathepsins in this process.


1984 ◽  
Vol 159 (1) ◽  
pp. 57-67 ◽  
Author(s):  
L LeFrancois ◽  
M J Bevan

We have investigated which T cell subclass defined by cytolysis with monoclonal anti-Lyt-1.2 and anti-Lyt-2.2 antibodies is required to adoptively transfer the ability to reject skin grafts. B6.Thy-1.1 spleen cells immune to graft antigens were fractionated with antibody plus C' and transferred to adult thymectomized, irradiated, bone marrow-reconstituted (ATXBM) B6.Thy-1.2 hosts that were simultaneously grafted with BALB.B skin. We found that when the ATXBM hosts were used 6 wk after irradiation and marrow reconstitution, both Lyt-1-depleted and Lyt-2-depleted immune spleen cells could transfer the ability to promptly reject skin grafts. However, such ATXBM recipients of Lyt-2-depleted cells that had rejected skin grafts were found to contain graft-specific CTL that were largely of host (B6.Thy-1.2) origin. When ATXBM hosts were used for the experiment 1 wk after irradiation and marrow reconstitution, no host-derived graft-specific CTL could be detected. However, graft rejection occurred in recipients of anti-Lyt-1- or anti-Lyt-2 plus C'-treated immune cells and specific CTL were generated from spleen cells of both groups. Thus, in the absence of a host-derived response, adoptively transferred immune Lyt-2+ cells, either resistant to, or that escaped from, antibody plus C' treatment, are able to expand in response to the antigenic stimulus provided by the graft. A more complete elimination of specific T cell subclasses is therefore needed to assess the relative contribution of a particular subset to the graft rejection process.


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