Research
My research aims to define the role of neutrophil-endothelial cell interactions in regulating pulmonary inflammation. Much of our understanding of neutrophil-pulmonary vascular endothelial cell interaction, and the mechanisms underlying the recruitment of leukocytes into the lung, has been extrapolated from studies undertaken in the systemic circulation. However, substantial differences exist between the pulmonary and systemic circulations, including the site of leukocyte migration (pulmonary capillaries rather than post-capillary venules), the importance of physical entrapment of neutrophils in the lung microcirculation over adhesion/rolling events, and major differences in the repertoire of endothelial ligands expressed. I have previously demonstrated that the healthy human pulmonary vasculature plays a critical role in host defence by selectively trapping primed neutrophils, facilitating their de-priming, and later releasing them back into the pulmonary circulation in a quiescent state, and furthermore that this homeostatic mechanism fails in patients with acute respiratory distress syndrome (ARDS). I am currently delineating the critical neutrophil-endothelial cell interactions occurring during these processes, so we may better develop efficacious therapies for pulmonary inflammation in the critically ill.
Publications
Proudfoot AG, O’Kane CM, Bayliffe A, Serone A, Bareille PJ, Smith S, Brown V, Hamid UI, Wright T, Chen Y, Wilson R, Cordy J, van Wilte R, Morley P, Elborn JS, Hind M, Chilvers ER, Griffiths M, Summers C*, McAuley DF*. A domain antibody to the tumour necrosis factor receptor one (TNFR1) prevents pulmonary inflammation in experimental models of acute respiratory distress syndrome. Thorax 2018, in press. (* these authors contributed equally to this work).
Ekpenyong AE, Töpfner N, Fiddler C, Herbig M, Li W, Cojoc G, Summers C, Guck J, Chilvers ER. Mechanical deformation induces depolarisation of neutrophils. Science Advances, 2017; 3:e1602536
Juss JK, House D, Amour A, Begg M, Herre J Storisteanu DML, Hoenderdos K, Bradley G, Lennon M, Summers C, Hessel EM, Condliffe AM and Chilvers ER. ARDS neutrophils have a distinct phenotype and are resistant to phophoinositide 3-kinase inhibition. Am J Respir Crit Care Med, 2016; 194:961-973
Hoenderdos K, Lodge K, Hirst RA, Chen C, Palazzo SGC, Emerenciana A, Summers C, Angyal A, Porter L, Juss JK, O’Callaghan C, Chilvers ER, Condliffe AM. Hypoxia up-regulates neutrophil degranulation and potential for tissue injury. Thorax 2016; 71:1030-1038
Summers C, Singh NR, White JF, Mackenzie IM, Johnston A, Solanki C, Balan KK, Peters AM, Chilvers ER. Pulmonary retention of primed neutrophils: a novel protective host response, which is impaired in acute respiratory distress syndrome. Thorax 2014; 69:623-629.
Summers C, Chilvers ER, Peters AM. Mathematical modelling supports the presence of neutrophil de-priming in vivo. Physiological Reports 2014; 2:e00241
Singh N, Johnston A, Peters AM, Babar J, Chilvers ER, Summers C. Acute lung injury results from failure of neutrophil de-priming: a new hypothesis. Eur J Clin Invest 2012; 42: 1342-1349.
Cowburn AS, Summers C, Dunmore BJ, Farahi N, Hayhoe RP, Print CG, Cook SJ, Chilvers ER. GM-CSF causes a paradoxical increase in the BH3-only protein Bim in human neutrophils. Am J Respir Cell Mol Biol 2011; 44: 879-887.
McGovern NN, Cowburn AS, Porter L, Walmsley SR, Thompson AA, Summers C, Willcocks LC, Whyte MKB, Condliffe AM, Chilvers ER. Hypoxia inhibits respiratory burst activity and killing of staphylococcus aureus in human neutrophils. J Immunol 2011; 186: 453-463.
Summers C, Rankin SM, Condliffe AM, N Singh, Peters AM, ER Chilvers. Neutrophil kinetics in health and disease. Trends Immunol 2010; 31:318-324.
Cowburn AS, Macias D, Summers C, Chilvers ER, Johnson RS. Cardiovascular adaptation to hypoxia and the role of peripheral resistance. eLife 2018, in press.
Desautels T, Das R, Calvert J, Trivedi M, Summers C, Wales D, Ercole A. Prediction of early unplanned intensive care unit readmission in a UK tertiary-care hospital: A cross-sectional machine learning approach. BMJ Open 2017, in press.
Summers C, Singh NR, Worpole L, Simmonds R, Babar J, Condliffe AM, Gunning KE, Johnston AJ, Chilvers ER. Incidence and recognition of acute respiratory distress syndrome in a UK intensive care unit. Thorax 2016; 71:1050-1051.
Millar FR, Summers C, Griffiths MJ, Toshner MR, Proudfoot AG. The pulmonary endothelium in the Acute Respiratory Distress Syndrome – insights and therapeutic opportunities. Thorax 2016; 71:462-473.
Proudfoot AG and Summers C. Killing without collateral damage: A new hope for sepsis therapy. Immunol Cell Biol 2014; 94:739-40.
Farahi N, Singh NR, Heard S, Loutsios C, Summers C, Simmonds RP, Solanki CK, Solanki K, Balan KK, Ruparelia P, Peters AM, Condliffe AM, Chilvers ER. Use of 111-Indium-labelled autologous eosinophils to establish the in vivo kinetics of human eosinophils in healthy subjects. Blood 2012; 120: 4068-4071.
Szczepura KR, Ruparelia P, Solanki CK, Balan KK, Newbold P, Summers C, Chilvers ER, Peters AM. Measuring whole-body neutrophil redistribution using a dedicated whole body counter and ultra-low doses of 111Indium (whole body counting). Eur J Clin Invest 2011; 41: 77-83.
White JF, Cowburn AS, Summers C, Cadwallader KA, Mackenzie I, Prasaedom RJ, Peters AM, Chilvers ER. The influence of the spleen on neutrophil apoptosis in vivo. J Cell Death 2011; 4: 1-5.
Ruparelia P, Szczepura K, Summers C, Solanki CK, Balan KK, Newbold P, Bilton D, Peters AM, Chilvers ER. Quantification of 111In-neutrophil migration into the lungs of patients with chronic obstructive pulmonary disease. Eur J Nucl Med Mol Imaging 2011; 38: 911-919.
Ruparelia P, Szczepura K, Summers C, Peters AM, Chilvers ER. 99mTechnetium-labelled neutrophil scanning in pneumonia. Thorax 2009; 64:92.
Gooptu B, Miranda E, Nobeli I, Mallya M, Purkiss A, Leigh-Brown SC, Summers C, Phillips RL, Lomas DA, Barrett TE. Crystallographic and cellular characterisation of two mutations stabilising the native fold of alpha1-antitrypsin: implications for rational drug design. J Mol Biol 2009; 387:857-68.
Cowburn AS, Condliffe AM, Farahi N, Summers C, Chilvers ER. Advances in neutrophil biology: clinical implications. Chest 2008; 134: 606-612.
Durrington HJ, Summers C. Recent changes in the management of community acquired pneumonia. Brit Med J 2008; 336:1429-1433.
Enoch DA, Summers C, Brown NM, Moore L, Gillham MI, Burnstein RM, Thaxter R, Enoch LM, Matta B, Sule O. Investigation and management of an outbreak of multidrug-carbapenem-resistant Acinetobacter baumannii in Cambridge, UK. J Hosp Infect 2008; 70:109-118.
