Images from a SPECT/CT study of a patient with lung cancer using 111-indium radiolabelled granulocytes 1 of 2
Confocal microscopy image showing neutrophils that have phagocytosed staphylococcus aureus (nucleus – blue, cytoskeleton – red, Staph aureus – green). 2 of 2
Research
The Summers laboratory is split between the Divisions of Respiratory Medicine and Anaesthesia, and studies the role of the innate immune system in acute and chronic inflammation.
Neutrophils are the principal effectors of the innate immune response and play a crucial role in host defence against invading microbes. Hence, patients displaying a defect in either the number or function of these cells are highly vulnerable to recurrent and often fatal bacterial and fungal infection. To perform their bactericidal functions efficiently neutrophils need to be highly mobile, responsive to the finest of chemotactic trails, and fully ‘armed’ to permit efficient intracellular killing. Mechanisms are also needed to prevent premature or excessive activation, and to allow efficient removal of cells at the termination of the inflammatory response. Failure of any one of these processes can lead to prolonged residency and activation of neutrophils within tissues, and the uncontrolled release of an array of noxious granule proteins and pro-inflammatory mediators. The histotoxic nature of many of these agents has been strongly implicated in inflammatory disorders including acute respiratory distress syndrome (ARDS), bronchiectasis, fatal asthma, ischaemia-reperfusion injury, and chronic obstructive pulmonary disease (COPD).
Neutrophil priming is an event whereby the response of the cell to an activating stimulus is augmented greatly by prior exposure to a priming agent (eg. LPS, TNF) and is a critical determinant of the pathogenic capacity of these cells in vivo. My group revealed for the first time that priming of human neutrophils is reversible in vivo, refuting the view that priming is a terminal event. Using 111-Indium and 99m-Technicium-labelled autologous granulocytes we made the first measurements of single pass neutrophil transit across the lung in humans; these confirmed substantial initial retention of ex-vivo primed cells by the pulmonary circulation followed by slow but complete release, supporting our hypothesis that the healthy pulmonary vasculature can retain primed neutrophils, facilitate their depriming and later release them into the systemic circulation in a quiescent deprimed state.
We have extended our studies using radiolabelled granulocytes to investigate the role of neutrophils in idiopathic pulmonary fibrosis and lung cancer, and monocytes in lung injury and other chronic inflammatory disorders.
To see details of our Critical Care-related research programme please see http://anaesthetics.medschl.cam.ac.uk/ccg/