RT Journal Article SR Electronic T1 Phospholipase C Activator m-3M3FBS Protects against Morbidity and Mortality Associated with Sepsis JF The Journal of Immunology JO J. Immunol. FD American Association of Immunologists SP 2000 OP 2005 DO 10.4049/jimmunol.1200635 VO 189 IS 4 A1 Kim, Sang Doo A1 Kim, Hak Jung A1 Shim, Jae Woong A1 Lee, Ha Young A1 Lee, Sung Kyun A1 Kwon, Soonil A1 Jung, Young Su A1 Baek, Suk-Hwan A1 Park, Joon Seong A1 Zabel, Brian A. A1 Bae, Yoe-Sik YR 2012 UL http://www.jimmunol.org/content/189/4/2000.abstract AB Although phospholipase C (PLC) is a crucial enzyme required for effective signal transduction and leukocyte activation, the role of PLC in polymicrobial sepsis remains unclear. In this study, we show that the direct PLC activator m-3M3FBS treatment significantly attenuates vital organ inflammation, widespread immune cell apoptosis, and mortality in a mouse sepsis model induced by lethal cecal ligation and puncture challenge. Mechanistically, m-3M3FBS–dependent protection was largely abolished by pretreatment of mice with the PLC-selective inhibitor U-73122, thus confirming PLC agonism by m-3M3FBS in vivo. PLC activation enhanced the bactericidal activity and hydrogen peroxide production of mouse neutrophils, and it also enhanced the production of IFN-γ and IL-12 while inhibiting proseptic TNF-α and IL-1β production in cecal ligation and puncture mice. In a second model of sepsis, PLC activation also inhibited the production of TNF-α and IL-1β following systemic LPS challenge. In conclusion, we show that agonizing the central signal transducing enzyme PLC by m-3M3FBS can reverse the progression of toxic shock by triggering multiple protective downstream signaling pathways to maintain organ function, leukocyte survival, and to enhance microbial killing.