It appears you don't have support to open PDFs in this web browser. To view this file, Open with your PDF reader
Abstract
Triggering receptor expressed on myeloid cells (TREM)-1 on polymorphonuclear neutrophils (PMN) regulates innate immune activation in infectious and non-infectious conditions. TREM-1 ligation activates phosphatidyl-inositol 3 kinase (PI3K) triggering all neutrophil effector functions. As idelalisib is a PI3K inhibitor in clinical use for the treatment of non-Hodgkin lymphomas, we asked whether this inhibitor affects PMN functionalities. We analyzed PMNs from healthy donors or lymphoma patients for oxidative burst, phagocytosis, activation markers and IL-8 release upon TREM-1 or TLR ligation ex vivo. In addition, we performed western blot analyses to characterize the signaling events inhibited by idelalisib and other PI3K inhibitors. Upon TREM-1 ligation, the oxidative burst, degranulation, L-selectin shedding and cytokine release were all strongly reduced in the presence of idelalisib along impaired phosphorylation of P38, AKT and ERK by western blot analyses. In line with this, PMNs from patients receiving idelalisib also displayed an impaired TREM-1 mediated PMN activation ex vivo. In conclusion, PI3K inhibitors might cause a neutropenia-like susceptibility to infections in patients by leading to impaired PMN functionality. This should be considered when evaluating patients for infections treated with such inhibitors in daily clinical routine.
You have requested "on-the-fly" machine translation of selected content from our databases. This functionality is provided solely for your convenience and is in no way intended to replace human translation. Show full disclaimer
Neither ProQuest nor its licensors make any representations or warranties with respect to the translations. The translations are automatically generated "AS IS" and "AS AVAILABLE" and are not retained in our systems. PROQUEST AND ITS LICENSORS SPECIFICALLY DISCLAIM ANY AND ALL EXPRESS OR IMPLIED WARRANTIES, INCLUDING WITHOUT LIMITATION, ANY WARRANTIES FOR AVAILABILITY, ACCURACY, TIMELINESS, COMPLETENESS, NON-INFRINGMENT, MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. Your use of the translations is subject to all use restrictions contained in your Electronic Products License Agreement and by using the translation functionality you agree to forgo any and all claims against ProQuest or its licensors for your use of the translation functionality and any output derived there from. Hide full disclaimer