Removal of Apoptotic Cells and Its Consequences

• The Inflammatory Process:
• Mechanisms of initiation of inflammation
• Emigration, maturation and secretion from inflammatory cells
• Removal of inflammatory cells, apoptosis and repair
• Mediators of Inflammation:

• Production and intracellular and extracellular roles of lipid mediators, chemokines and cytokines

• Inflammatory Processes and Disease:

• Leukocyte involvement in ARDS, airways reactivity (Asthma), Cystic Fibrosis, Bronchiectasis and Interstitial Lung Disease

• Control of inflammatory disease processes by removal of apoptotic inflammatory cells

• Membrane lipid alterations in cell activation and apoptosis
• Isolation of leukocytes, labeling, and kinetic studies in vivo and in vitro
• Animals models of lung disease

• Frasch SC, Henson PM, Kailey JM, Richter DA, Janes MS, Fadok VA, Bratton DL. Regulation of phospholipid scramblase activity during apoptosis and cell activation by PKC delta. J Biol Chem. 275(30):23065-23073, 2000.

• Fadok VA, Bratton DL, Rose D, Pearson A, Ezekowitz A, Henson PM. A receptor for phosphatidylserine-specific clearance of apoptotic cells. Nature 405:85-90, 2000.

• Whitlock BB, Gardai S, Fadok V, Bratton D, Henson PM. Differential roles for alpha m beta 2 integrin clustering or activation in the control of apoptosis via regulation of Akt and ERK survival mechanisms. J Cell Biol. 151:1305-1320, 2000.

• Taylor PR, Carugati A, Fadok VA, Cook HT, Andrews M, Carroll MC, Savill JS, Henson PM, Botto M, Walport MJ. A heirarchical role for classical pathway complement proteins in the clearance of apoptotic cells in vivo: a mechanism for protection from autoimmunity. J Exp Med. 192:359-366, 2000.

• Bowers RC, Hevko J, Henson PM, Murphy RC. A novel glutathione containing eicosanoid (FOG7) chemotactic for human granulocytes. J Biol Chem 275(39):29931-29934, 2000.

The inflammatory process, manifest in everyone’s experience as the local reaction of the skin to a splinter, represents a nonspecific response of all the tissues of the body to injury. It is a complex, interacting network of dynamic processes involving the white cells of the blood and the blood vessels of the particular tissue or organ. Generally the effects of inflammation are beneficial, leading to removal of the injurious stimulus, repair and recovery of function. However, inflammatory processes also contribute to many human diseases including the lung diseases, asthma, emphysema, interstitial lung disease and Adult Respiratory Distress Syndrome (ARDS). We seek to understand the basic mechanisms of the inflammatory process in the lung, in particular the elements that control these effects and lead to their normal resolution so that therapeutically we can harness the beneficial aspects (protection) and minimize the detrimental sides of the processes, i.e. chronic pulmonary disease.

  To top of page