Volatile anesthetics (VAs) have been in clinical use for a very long time. Their mechanism of action is yet to be fully delineated, but multiple ion channels have been reported as targets for VAs (canonical VA targets). It is increasingly recognized that VAs also manifest effects outside the central nervous system, including on immune cells. However, the literature related to how VAs affect the behavior of immune cells is very limited, but it is of interest that some canonical VA targets are reportedly expressed in immune cells. Here, we review the current literature and describe canonical VA targets expressed in leukocytes and their known roles. In addition, we introduce adhesion molecules called β2 integrins as noncanonical VA targets in leukocytes. Finally, we propose a model for how VAs affect the function of neutrophils, macrophages, and natural killer cells via concerted effects on multiple targets as examples.

Sepsis continues to be associated with high morbidity and mortality. Currently, sepsis is managed only conservatively. In sepsis, a substantial number of neutrophils is required, leading to accelerated neutrophil production. Immature neutrophils are released into the circulation to meet a demand, despite their less effective functioning in microbial eradication. Although an intervention to provide more mature neutrophils may serve as a potential sepsis treatment, the mechanism of neutrophil differentiation and maturation remains poorly understood. We discovered that CD11c, traditionally known as a dendritic cell marker, was expressed in neutrophils and regulated neutrophil maturation and effector functions. In the absence of CD11c, neutrophil maturation was impaired in the bone marrow, concomitant with a significant increase in the proliferation and apoptosis of preneutrophils, associated with less effector functions. Under lipopolysaccharide challenge, inducing an emergent neutrophil production in the bone marrow, CD11c deficiency exaggerated the release of immature neutrophils into the circulation, associated with a significant proliferation and apoptosis of preneutrophils. In contrast, constitutively active CD11c knock-in mice showed accelerated neutrophil maturation associated with enhanced effector functions, which further supports the notion that CD11c regulates neutrophil maturation. Furthermore, the constitutively active CD11c knock-in mice offered enhanced bacterial eradication. Taken together, we discovered that CD11c was critical for the regulation of neutrophil maturation, and CD11c activation could serve as a potential target for sepsis treatment.