Characterization of Neutrophil Subsets in Healthy Human Pregnancies

Ssemaganda, Aloysius; Kindinger, Lindsay; Bergin, Philip; Nielsen, Leslie; Mpendo, Juliet; Ssetaala, Ali; Kiwanuka, Noah; Munder, Markus; Teoh, Tiong Ghee; Kropf, Pascale; Müller, Ingrid

doi:10.1371/journal.pone.0085696

Cited by 62 publications

(79 citation statements)

References 31 publications

(46 reference statements)

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“…Neutrophils represent a highly heterogeneous cell population. The cytometric approach allows for cell subsets (different phenotypes and function) to be differentiated in various clinical and experimental settings (e.g., during labor and in both maternal and cord blood) (30,31). In the present study, cells that showed high-intensity fluorescence (rho+) accounted for 5-7% of unstimulated neutrophils; this proportion corresponds to previous reports (32).…”

Section: Discussionsupporting

confidence: 84%

Effects of local anesthetics on the respiratory burst of cord blood neutrophils in vitro

et al. 2016

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Background: Whether local anesthetics exert anti-inflammatory effects in fetal and newborn systemic neutrophils is unclear. The aim of the present study was to assess the effects of bupivacaine and lidocaine on the respiratory burst of cord blood neutrophils in vitro compared with adult cells. Methods: Whole cord blood (n = 12) and control adult blood samples (n = 7) were incubated with bupivacaine (0.0005, 0.005, 0.05, 1 mmol/l) and lidocaine (0.002, 0.02, 0.2, 4 mmol/l) for 1 and 4 h. The production of reactive oxygen species (ROS) by unstimulated neutrophils and the phorbol myristate acetate-induced oxidative burst were assessed by flow cytometry. A subset of neutrophils showing high fluorescence intensity (rho+) was analyzed separately. results: After 1 h incubation, local anesthetics decreased the respiratory burst in whole cord blood and adult neutrophils in a similar manner. At the clinically relevant concentration of 0.0005 mmol/l, bupivacaine was active, but its effect in cord blood cells could not be detected after 4 h. The cord blood rho+ cell subset was unresponsive to the inhibitory action of bupivacaine. In rho+ neutrophils, basal ROS production was stimulated by lidocaine at the lowest concentration tested. conclusion: Bupivacaine and lidocaine can decrease the respiratory burst in neutrophils of term newborns. t he question of the effects of local anesthetics (LAs) on fetal neutrophils arises in the clinical context of the broad application of neuraxial blockade in obstetrics. Epidural technics are the gold standard for labor intrapartum analgesia and are administered to parturients on request. By applying higher doses of LAs through the existing epidural catheter, surgical anesthesia for cesarean delivery may be easily obtained. The fetal and neonatal implications of epidural techniques are mostly considered to be indirect and dependent on modulation of maternal physiology, and are associated with a higher risk of neonatal pyrexia and sepsis evaluation, but not neonatal infection (1-3). The reasons for these findings are not sufficiently clear. However, direct fetal and neonatal effects of LAs as a result of placental drug transfer should not be entirely excluded. LAs administered epidurally enter the maternal systemic circulation and, after crossing the placental barrier, can reach the fetal circulation, with levels approximately one-third to half those seen in the maternal circulation. Furthermore, because of ion trapping and slower elimination, LAs may persist for longer in fetal and neonatal than maternal blood (4). LAs in the fetal systemic circulation have been reported to abolish an offspring's cardiovascular adaptive reaction to asphyxia (5) and have been suggested to affect blood cells. Specifically, bupivacaine has been shown to modify plasma membrane properties of fetal erythrocytes (6). In other studies, lidocaine, a prototypical amino-amide agent administered epidurally for cesarean sections, was suggested to be responsible for the inhibition of natural killer cells and neutrophil a...

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Section: Discussionsupporting

confidence: 84%

Effects of local anesthetics on the respiratory burst of cord blood neutrophils in vitro

et al. 2016

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“…Interestingly, in vitro activation of circulating neutrophils isolated from healthy donors induced the acquisition of the suppressive capacity and lowdensity properties probably after degranulation. 107 In line with these results, LDGs 101,103 and G-MDSCs 107 express high levels of CD66b, a receptor mobilized from the granules to the surface on cell activation. However, additional studies are needed to further clarify the exact origin of these cells and the external signals that confer their immunosuppressive capacities.…”

mentioning

confidence: 76%

“…68,98 Self-DNA and antimicrobial peptides present in the NET structures led to the generation of autoantibodies triggering a positive feedback loop that amplified the inflammatory response. Of note, LDGs have also been identified in other physiological or pathogenic immune alterations such as cancer, 99 sepsis, 100 pregnancy, 101 diabetes, 102 or HIV infection. 103 Interestingly, these LDG subpopulations share the ability to suppress the immune response, a characteristic that contrasts the proinflammatory phenotype of SLE-associated neutrophils.…”

mentioning

confidence: 99%

Neutrophil heterogeneity: implications for homeostasis and pathogenesis

Silvestre-Roig

Hidalgo

Soehnlein

2016

Blood

346

305

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Neutrophils are polymorphonuclear leukocytes of the phagocytic system that act as first line of host defense against invading pathogens but are also important mediators of inflammation-induced injury. In contrast to other members of the innate immune system, neutrophils are classically considered a homogenous population of terminally differentiated cells with a well-defined and highly conserved function. Indeed, their short lifespan, the absent proliferative capacity, their limited ability to produce large amounts of cytokines, and the failure to recirculate from the tissue to the bloodstream have sustained this idea. However, increasing evidence over the last decade has demonstrated an unexpected phenotypic heterogeneity and functional versatility of the neutrophil population. Far beyond their antimicrobial functions, neutrophils are emerging as decision-shapers during innate and adaptive immune responses. These emerging discoveries open a new door to understand the role of neutrophils during homeostatic but also pathogenic immune processes. Thus, this review details novel insights of neutrophil phenotypic and functional heterogeneity during homeostasis and disease.

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“…As recently reviewed, NET DNA can be found circulating under normal conditions, with levels enhanced during infection, inflammation, and cancer, i.e., in conditions where activation of coagulation is a prominent feature, pointing to NETs as contributing factors for thrombosis under both normal and pathological conditions. The issue of neutrophil subpopulations is also relevant when discussing NETs and thrombophilia, since low-density granulocytes (LDGs) increase in number with vasculitis (37), cancer (96), pregnancy (97), and infection (98). All of these conditions are associated with thrombophilia and with increased levels of NETs, possibly due to spontaneous intravascular NET formation from LDGs.…”

Section: Statins and Netsmentioning

confidence: 99%