My laboratory conducts research on acute lung injury (ALI), which is a syndrome produced by multiple causes including pneumonia, sepsis, trauma, and the transfusion of blood products. ALI is responsible for 75,000 deaths in the U.S. each year and yet there is no effective pharmacotherapy to treat these patients. We are focused on the mechanisms responsible for lung endothelial permeability, which is the hallmark of ALI.
We have centered our interests on the role of platelets in lung inflammation and injury. Platelets are increasingly recognized as active participants in inflammatory diseases and part of the coordinated innate immune response. We have developed a mouse model of transfusion-related acute lung injury (TRALI) and discovered that this model is both platelet and neutrophil-dependent. We are exploring how platelets are mediating injury in TRALI and other in vivo models of ALI (LPS, acid-induced, ischemia-reperfusion) including the role of neutrophil extracellular traps (NETs).
In conjunction with the Krummel laboratory at UCSF, we have also developed a method to image the lung microcirculation using two-photon intravital microscopy. Using a variety of transgenic fluorescent mouse strains, we are defining the migration and interactions of immune cells and platelets in the lung under normal and injury conditions.
Finally, we are one of the few centers in the U.S. to establish a mouse lung transplantation model that we are using to study mechanisms of both early graft dysfunction (similar to ALI) and late graft dysfunction (obliterative bronchiolitis). Lung transplantation has one of the lowest median survivals among all solid organ transplantations and we are dedicated to defining the lung-specific alloimmune responses that mediate rejection.
Looney MR, Thornton EE, Sen D, Lamm WJ, Glenny RW, Krummel MF. Stabilized imaging of immune surveillance in the mouse lung. Nat Methods 8(1):91-96, 2011.
Looney MR, Matthay MA. Neutrophil sandwiches injure the microcirculation. Nat Med 15(4):364-366, 2009.
Looney MR, Nguyen JX, Hu Y, Van Ziffle JA, Lowell CA, Matthay MA. Platelet depletion and aspirin treatment protect mice in a two-event model of transfusion-related acute lung injury. J Clin Invest 119(11):3450-3461, 2009.
Looney MR, Esmon CT, Matthay MA. The role of coagulation pathways and treatment with activated protein C in hyperoxic lung injury. Thorax 64(2):114-120, 2009.
Su X, Johansen ML, Looney MR, Brown EJ, Matthay MA. CD47 deficiency protects mice from LPS-induced acute lung injury and E. coli pneumonia. J Immunol 180(10):6947-6953, 2008.
Looney MR, Su X, Van Ziffle JA, Lowell CA, Matthay MA. Neutrophils and their Fcγ receptors are essential in a mouse model of transfusion-related acute lung injury. J Clin Invest 116(6):1615-1623, 2006.