IMMATURE CIRCULATING NEUTROPHILS IN SEPSIS HAVE IMPAIRED PHAGOCYTOSIS AND CALCIUM SIGNALING
- 1 December 2008
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Shock
- Vol. 30 (6), 618-622
- https://doi.org/10.1097/shk.0b013e318173ef9c
Abstract
Patients with sepsis commonly develop leukocytosis, which is presumed to reflect a host response to infection. Effective phagocytosis by neutrophils is crucial in the clearance of invading microbes. However, efficacy of phagocytosis in sepsis is controversial. We hypothesized that host phagocytic capacity in sepsis can be affected by immature neutrophils that are released into the circulation. Circulating neutrophils were evaluated in 16 patients with severe sepsis and 5 healthy donors. Immature neutrophils were identified by the cell morphology. Phagocytosis was evaluated by micromanipulation technique and simultaneous cytosolic-free Ca2+ imaging. Leukocytosis was present in 12 of 16 patients. Nine of the 12 patients with leukocytosis and 3 of 4 patients with normal white blood cell counts had increased circulating immature neutrophils (mean, 39.3% +/- 20.7%; normal <or=5%). Quantification of the phagocytic activity revealed a significantly reduced phagocytic index of immature neutrophils as compared with mature neutrophils from both sepsis patients and healthy donors (25% +/- 5% vs. 69% +/- 8% and 42% +/- 6%; P < 0.05). As compared with mature neutrophils, the number of internalized zymosan particles within immature neutrophils was also significantly lower. Mature neutrophils from patients and healthy donors displayed a single rapid transient Ca signal during phagocytosis in contrast with weak signals from immature neutrophils. Our preliminary results show that phagocytic capacity of immature neutrophils is lower as compared with mature neutrophils. An increase in immature neutrophils in severe sepsis may undermine the overall phagocytic efficacy of a host despite observed leukocytosis.Keywords
This publication has 32 references indexed in Scilit:
- POLYMORPHONUCLEAR LEUKOCYTE DYSFUNCTION SYNDROME IN PATIENTS WITH INCREASING SEPSIS SEVERITYShock, 2006
- Localised PtdIns(3,4,5)P3 or PtdIns(3,4)P2 at the phagocytic cup is required for both phagosome closure and Ca2+ signalling in HL60 neutrophilsJournal of Cell Science, 2006
- Leukocyte Count as an Independent Predictor of Recurrent Ischemic EventsStroke, 2004
- Phagosomal oxidative activity during β2 integrin (CR3)-mediated phagocytosis by neutrophils is triggered by a non-restricted Ca2+signal: Ca2+ controls time not spaceJournal of Cell Science, 2003
- Cytosolic free Ca2+ changes and calpain activation are required for β integrin–accelerated phagocytosis by human neutrophilsThe Journal of cell biology, 2002
- The involvement of nitric oxide in the anti‐Candida albicans activity of rat neutrophilsImmunology, 1996
- Effect of extracorporeal membrane oxygenation on neutrophil function in neonatesCritical Care Medicine, 1993
- Definitions for Sepsis and Organ Failure and Guidelines for the Use of Innovative Therapies in SepsisChest, 1992
- Oxidase activation in individual neutrophils is dependent on the onset and magnitude of the Ca2+ signalCell Calcium, 1990
- Proliferative Potentials of Bone Marrow and Blood Cells Studied by in vitro Uptake of H3-ThymidineActa Haematologica, 1959