Participation of Monocyte Subpopulations in Progression of Experimental Endotoxemia (EE) and Systemic Inflammation

Abstract

Systemic inflammation plays a crucial role in formation of various pathological conditions, including sepsis, burns, and traumas. The main effector cells participating in progression of systemic inflammation response and sepsis are monocytes, which regulate both innate and acquired immunity via phagocytosis, synthesis of cytokines and chemokines, antigen presentation, and lymphocyte activation. Thus, the monocytes are considered as a link between innate and acquired immunity. The monocyte subpopulations taken into consideration in the study essentially determine the progression of systemic inflammation and could serve as targets for therapeutic intervention. The complexity of the analysis of pathophysiology of systemic inflammation lies in its high variability conditioned by individual peculiarities of the patients and inflammation progression specifications. To overcome these limitation, model of experimental endotoxemia (EE) is used. The results of EE, in turn, cannot be directly extrapolated on patients with the systemic inflammatory response. This review is dedicated to discussing the role of monocyte subpopulations in progression of systemic inflammation/sepsis and EE.

Figure 1

Human monocyte subsets in health. Human monocytes mature in the bone marrow and are subsequently released into the circulation as CD14++classical monocytes. Progressively, classical monocytes (CD14++CD16−) give rise to nonclassical monocytes (CD14dimCD16++) through an intermediate step of CD14 + CD16+ monocytes. MP: myelomonocytic progenitor; CM: classical monocytes; IM: intermediate monocytes; NCM: nonclassical monocytes.

Figure 2

Monocytes in experimental endotoxemia. Total monocyte percentages (a) are decreased at 1–1.5 h after LPS injection, and cell count increases at 6–8 h after LPS injection. Monocyte subset percentages (b) show that classical monocytes (cMo) comprise 80–90% of all monocytes. cMo percentages follow those of total monocytes. Intermediate monocyte (iMo) and nonclassical monocyte (ncMo) percentages are decreased 1–8 h after LPS injection with a trend towards higher iMo percentage at 24 h after LPS injection [7, 8].

Figure 3

Expression of cytokines by subpopulations of monocytes after LPS activation. ^∗The cytokines expressed mainly by this subpopulation of monocytes. MP: myelomonocytic progenitor; CM: classical monocytes; IM: intermediate monocytes; NCM: nonclassical monocytes.