The fate and lifespan of human monocyte subsets in steady state and systemic inflammation

Abstract

Using stable isotope labeling, Patel et al. establish the lifespan of all three human monocyte subsets that circulate in dynamic equilibrium; in steady state, classical monocytes are short-lived precursors with the potential to become intermediate and nonclassical monocytes. They highlight that systemic inflammation induces an emergency release of classical monocytes into the circulation.

Current best estimates for the average lifespans of mouse and human leukocytes: reviewing two decades of deuterium‐labeling experiments

“…Both studies found that deuterium first accumulated in CM, and subsequently appeared in IM and later in NCM, which confirmed the established linear differentiation scheme . Patel et al beautifully re‐confirmed this pathway more directly by performing monocyte depletion experiments in humans and adoptive transfer experiments in humanized mice.…”

“…Monocytes are heterogeneous, however, and have been subdivided into classical CD14 ++ CD16 − (CM), intermediate CD14 ++ CD16 + (IM), and non‐classical CD14 + CD16 ++ monocytes (NCM). The residence times of monocytes in these three subpopulations have recently been investigated in two independent D 2 ‐glucose labeling studies …”

“…For these reasons, when we review studies based on short‐term overnight glucose labeling, we will not interpret the absolute values of the reported turnover rates, and only compare their relative values within each study. Importantly, while 1 or 2 days of labeling has its complexities and may be too short to reliably measure the turnover rates of populations of lymphocytes that are turning over at a time scale of months to years, the rapidity of glucose turnover makes D 2 ‐glucose labeling the method of choice for estimating the turnover rates of rapidly turning over populations, like monocytes and neutrophils …”

“…It may go wrong in the case of monocytes and neutrophils, where it is hard to distinguish whether short‐lived cells in the blood are produced by slowly cycling cells in the bone marrow, or whether longer lived cells in the blood are produced by rapidly cycling cells in the bone marrow (see Figure ). Estimating the lifespan of cells in populations that are maintained by a source typically requires models that explicitly describe the labeling of the precursor cells in the source, but also labeling data from that source. This issue is further addressed in Box 1 and we discuss it below.…”

Social Stress Mobilizes Hematopoietic Stem Cells to Establish Persistent Splenic Myelopoiesis

“…We found that this persistent vulnerability was mediated by a long-lasting pool of releasable monocytes in the spleen. This extended immunologic impact could not be explained by any extended change in bone marrow myelopoiesis (Wohleb et al, 2014), nor could this be explained by the persistence of a stress-induced bolus of long-lived monocytes (Yona et al, 2013; Patel et al, 2017). We hypothesized that the protracted oversupply of splenic monocytes may be mediated by the induction of extramedullary myelopoiesis in the spleen following stress.…”