Investigators have also described a CD28/CTLA4 independent ligand for CD86, which may also modulate our system both signaling via the receptor and ligand. Addressing both of these possibilities will be the subject of further studies. Finally, it is highly probable, that the role of CD86 may indeed be tissue compartment specific. In our previous study, we noticed differential regulation of CD86 in blood and peritoneal lavage. This most likely explains the differential cytokine response, especially IL-10, between these differing compartments. However, we are still unable to provide a mechanism for this differential compartment specific regulation. However, there are many important limitations to our study. Most notably is the use of a highly Arteether citations lethal form of polymicrobial sepsis in our murine model. It is well established that there are multiple phases to the immune response in sepsis, with the early phases dominated by massive pro-inflammatory cytokine production, and the latter phase by immunoparalysis. It is likely, that during the transition to these latter stages, a more prominent role for CD86 could be observed. In addition, the mechanism for loss of CD86 expression also remains incompletely understood. Whether this results in a true loss of expression or recruitment of additional low expressing CD86 monocytes from the bone marrow is also unclear. Future studies will be required to address these questions. Finally, while our data now suggest IRAK-M may be capable of differentially regulating CD80 and CD86 mediated cellular activation, there are still multiple limitations to this data. Most notably, is we can not explain the reason for the differential affinity for CD80 and CD86 for IRAK-M under resting or stimulated conditions. Understanding the reasons for this and the true biological significance of this association will be the subject of future studies detailing all members of the NF-kB signaling complex. In conclusion, we document a pivotal role for CD28-CD80 interaction in regulating the lethality of the acute phases of sepsis and septic shock. This occurs predominantly 121104-96-9 through the interaction between CD80 and CD28. These data suggest that any future therapies targeting this system in sepsis be directed specifically at CD80. The development and use of animal chronic obstructive pulmonary disease models requires sensitive methods of monitoring and quantifying the disease progression. Key components of COPD, as defined by the American Thoracic Societ
