Kinetics of Neutrophil Subsets in Acute, Subacute, and Chronic Inflammation

At homeostasis the vast majority of neutrophils in the circulation expresses CD16 and CD62L within a narrow expression range, but this quickly changes in disease. Little is known regarding the changes in kinetics of neutrophils phenotypes in inflammatory conditions. During acute inflammation more heterogeneity was found, characterized by an increase in CD16dim banded neutrophils. These cells were probably released from the bone marrow (left shift). Acute inflammation induced by human experimental endotoxemia (LPS model) was additionally accompanied by an immediate increase in a CD62Llow neutrophil population, which was not as explicit after injury/trauma induced acute inflammation. The situation in sub-acute inflammation was more complex. CD62Llow neutrophils appeared in the peripheral blood several days (>3 days) after trauma with a peak after 10 days. A similar situation was found in the blood of COVID-19 patients returning from the ICU. Sorted CD16low and CD62Llow subsets from trauma and COVID-19 patients displayed the same nuclear characteristics as found after experimental endotoxemia. In diseases associated with chronic inflammation (stable COPD and treatment naive HIV) no increases in CD16low or CD62Llow neutrophils were found in the peripheral blood. All neutrophil subsets were present in the bone marrow during homeostasis. After LPS rechallenge, these subsets failed to appear in the circulation, but continued to be present in the bone marrow, suggesting the absence of recruitment signals. Because the subsets were reported to have different functionalities, these results on the kinetics of neutrophil subsets in a range of inflammatory conditions contribute to our understanding on the role of neutrophils in health and disease.

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

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.