IMMATURE CIRCULATING NEUTROPHILS IN SEPSIS HAVE IMPAIRED PHAGOCYTOSIS AND CALCIUM SIGNALING

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Abstract

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 ≤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 Ca2+ 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.

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