PT  - JOURNAL ARTICLE
AU  - Hutchins, Noelle
AU  - Borgerding, Joshua
AU  - Chung, Chun-Shiang
AU  - Ayala, Alfred
TI  - Liver sinusoidal endothelial cells undergo apoptosis during sepsis, leading to organ dysfunction. (54.13)
DP  - 2011 Apr 01
TA  - The Journal of Immunology
PG  - 54.13--54.13
VI  - 186
IP  - 1 Supplement
4099  - http://www.jimmunol.org/content/186/1_Supplement/54.13.short
4100  - http://www.jimmunol.org/content/186/1_Supplement/54.13.full
SO  - J. Immunol.2011 Apr 01; 186
AB  - Sepsis is the leading cause of death in critically ill patients, and treatment options are limited. Our laboratory studies polymicrobial sepsis in murine models, and uses the liver as a model organ to investigate the disease’s pathophysiology. The liver, characterized as an immune tolerant organ, is susceptible to septic induced inflammation. We have previously reported that there is a twofold increase in the number of liver CD8+ T cells, 24 hours following cecal ligation and puncture (CLP—a surgical procedure that generates sepsis in mice). Since activated T lymphocytes must transverse the endothelium to reach the site of infection, it is possible that they directly interact with LSECs, and mediate liver injury through Fas-mediated apoptosis. This led us to hypothesize that as CD8+ T cells directly interact with LSECs, endothelial cell dysfunction occurs. Our preliminary results indicate that septic liver CD8+ T cells have cytotoxic effects on endothelial monolayer integrity, and release pro-inflammatory cytokines when directly co-cultured with CRL-2167, a murine endothelial cell line. We have also observed through flow cytometry that LSECs (CD146+/CD45- and CD31+/CD45- populations) have an increased expression of CD54 (ICAM-1), Fas, and Annexin V staining in vivo. These data suggest that CD8+ T cells directly interact with LSECs, alter the tolerance capacity of LSECs, and potentially kill LSECs through the Fas-FasL system, ultimately leading to liver organ injury in sepsis.