Pulmonary retention of primed neutrophils: a novel protective host response, which is impaired in the acute respiratory distress syndrome.
BACKGROUND
Acute respiratory distress syndrome (ARDS) affects over 200000 people annually in the USA. Despite causing severe, and often refractory, hypoxaemia, the high mortality and long-term morbidity of ARDS results mainly from extra-pulmonary organ failure; however the mechanism for this organ crosstalk has not been determined.


METHODS
Using autologous radiolabelled neutrophils we investigated the pulmonary transit of primed and unprimed neutrophils in humans. Flow cytometry of whole blood samples was used to assess transpulmonary neutrophil priming gradients in patients with ARDS, sepsis and perioperative controls.


RESULTS
Unprimed neutrophils passed through the lungs with a transit time of 14.2 s, only 2.3 s slower than erythrocytes, and with <5% first-pass retention. Over 97% of neutrophils primed ex vivo with granulocyte macrophage colony-stimulating factor were retained on first pass, with 48% still remaining in the lungs at 40 min. Neutrophils exposed to platelet-activating factor were initially retained but subsequently released such that only 14% remained in the lungs at 40 min. Significant transpulmonary gradients of neutrophil CD62L cell surface expression were observed in ARDS compared with perioperative controls and patients with sepsis.


CONCLUSIONS
We demonstrated minimal delay and retention of unprimed neutrophils transiting the healthy human pulmonary vasculature, but marked retention of primed neutrophils; these latter cells then 'deprime' and are re-released into the systemic circulation. Further, we show that this physiological depriming mechanism may fail in patients with ARDS, resulting in increased numbers of primed neutrophils within the systemic circulation. This identifies a potential mechanism for the remote organ damage observed in patients with ARDS.
Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, UK.
Charlotte
C
Summers
Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, UK.
Nanak R
NR
Singh
Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, UK.
Jessica F
JF
White
Department of Anaesthesia, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Iain M
IM
Mackenzie
Department of Anaesthesia, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Andrew
A
Johnston
Department of Nuclear Medicine, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Chandra
C
Solanki
Department of Nuclear Medicine, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
K K
KK
Balan
Department of Radiology, University of Cambridge School of Clinical Medicine, Cambridge, UK.
A Michael
AM
Peters
Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, UK.
Edwin R
ER
Chilvers
D001783:Blood Flow Velocity / Q000502:physiology; D002465:Cell Movement; D004912:Erythrocytes / Q000000981:diagnostic imaging / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000000981:diagnostic imaging / Q000502:physiology*; D010972:Platelet Activating Factor / Q000494:pharmacology; D011877:Radionuclide Imaging; D012128:Respiratory Distress Syndrome / Q000097:blood* / Q000000981:diagnostic imaging / Q000503:physiopathology*; D013147:Spirometry; D013667:Technetium / Q000493:pharmacokinetics; D013997:Time Factors
D007205:Indium Radioisotopes; D010972:Platelet Activating Factor; D013667:Technetium; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
ARDS; Neutrophil Biology