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Published on: July 10, 2013
C5a mediates peripheral blood neutrophil dysfunction in critically ill patients
Andrew Conway Morris1, Kallirroi Kefala, Thomas S Wilkinson
1Medical Research Council Centre for Inflammation Research, University of Edinburgh, Edinburgh, Scotland, UK.
Critically ill patients exhibit impaired neutrophil function, primarily due to activated complement. The inflamed lung also contributes to neutrophil dysfunction, independent of complement.
Area of Science:
- Critical care medicine
- Immunology
- Infectious disease
Background:
- Critically ill patients are prone to hospital-acquired infections.
- Neutrophil function in critical illness is not well understood.
Purpose of the Study:
- To characterize peripheral blood neutrophil (PBN) dysfunction in critically ill patients.
- To investigate the role of the inflamed lung in neutrophil phagocytic impairment.
Main Methods:
- Prospective collection of blood and bronchoalveolar lavage fluid from patients and volunteers.
- Laboratory analysis of neutrophil functions, including phagocytosis, migration, and bacterial killing.
Main Results:
- PBN phagocytic capacity was 36% lower in critically ill patients compared to healthy volunteers.
- Activated complement, specifically C3a and C5a, was strongly associated with impaired PBN phagocytosis.
- C5a impaired PBN phagocytosis, migration, and bacterial killing, while down-regulating CD88 expression.
- Leukocytes from bronchoalveolar lavage fluid also showed impaired function, and lavage supernatant reduced phagocytosis in healthy neutrophils.
Conclusions:
- Critically ill patients have significant PBN dysfunction mediated primarily by activated complement.
- The inflamed lung contributes to complement-independent neutrophil dysfunction.
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