Barr, L.*, Brittan, M.*, Conway Morris, A., McAuley, D. F., McCormack, C., Fletcher, A., Richardson, H., Connell, M., Patel, D., Wallace, W., Rossi, A. G., Davidson, D. J., Manson, L., Turner, M., Hirani, N., Walsh, T., Anderson, N., Dhaliwal, K., Simpson, A. J.
Am J Respir Crit Care Med. (2013) 188(4):449-55, Apr 29 [Epub ahead of print] PubMed
* denotes equal contribution
Davidson lab supported by funding from: MRC
Methods: Thirty healthy volunteers were enrolled in a randomized controlled trial. Volunteers inhaled lipopolysaccharide at baseline and were randomized to receive active mononuclear cell depletion by leukapheresis, or sham leukapheresis, in a double-blind fashion (15 volunteers per group). Serial blood counts were measured, bronchoalveolar lavage was performed at 9 hours, and [18F]fluorodeoxyglucose positron emission tomography at 24 hours. The primary end-point was the increment in circulating neutrophils at 8 hours.
Measurements and Main Results: As expected, inhalation of lipopolysaccharide induced neutrophilia and an up-regulation of inflammatory mediators in the blood and lungs of all volunteers. There was no significant difference between the depletion and sham groups in the mean increment in blood neutrophil count at 8 hours (6.16 x109/L and 6.15 x109/L respectively, P=1.00). Furthermore, there were no significant differences in bronchoalveolar lavage neutrophils or protein, positron emission tomography-derived measures of global lung inflammation or cytokine levels in plasma or bronchoalveolar lavage supernatant between the study groups. No serious adverse events occurred, and no symptoms were significantly different between the groups.
Conclusions: These findings do not support a role for circulating human monocytes in the early recruitment of neutrophils during lipopolysaccharide-mediated acute lung inflammation in humans.