Acute Lung Disease

Elevation of circulating heme triggers acute chest syndrome in transgenic sickle mice

Dr. Solomon Ofori-Acquah’s laboratory developed the first clinically relevant mouse model of acute chest syndrome by infusing purified hemin into sickle mice.

Ghosh S, Adisa OA, Chappa P, Tan F, Jackson KA, Archer DR, Ofori-Acquah SF. (2013). Extracellular hemin crisis triggers acute chest syndrome in sickle cell mice. J Clin Invest. 123(11):4809-20. PMID: 24084741. PMCID: PMC3809772. DOI: 10.1172/JCI64578.

Advanced high-resolution videomicroscopy of sickle cell mouse lungs

Dr. Prithu Sundd’s lab has developed advanced high-resolution videomicroscopy of sickle cell mouse lungs, which shows a role of inflammatory, adhesive mechanisms of acute cell aggregation and vaso-occlusion.

Bennewitz MF, Jimenez MA, Vats R, Tutuncuoglu E, Jonassaint J, Kato GJ, Gladwin MT, Sundd P. (2017). Lung vaso-occlusion in sickle cell disease mediated by arteriolar neutrophil-platelet microemboli. JCI Insight. 2(1):e89761. PMID: 28097236. PMCID: PMC5214368. DOI: 10.1172/jci.insight.89761.

Jimenez MA, Tutuncuoglu E, Barge S, Novelli EM, Sundd P. (2015). Quantitative microfluidic fluorescence microscopy to study vaso-occlusion in Sickle Cell Disease. Haematologica. 100(10):e390-3. PMID: 25975836. PMCID: PMC4591772. doi: 10.3324/haematol.2015.126631.

Bennewitz MF, Watkins SC, Sundd P. (2014). Quantitative intravital two-photon excitation microscopy reveals absence of pulmonary vaso-occlusion in unchallenged Sickle Cell Disease mice. IntraVital. 3(2):e29748. PMID: 25995970. PMCID: PMC4435611. doi: 10.4161/intv.29748.

Sundd P and Bennewitz MF. Leukocyte kinetics and migration in the lungs. in Hematologic Abnormalities and Acute Lung Syndromes (eds. Lee, J.S. & Donahoe, M.P.) 19-45 (Springer International Publishing, Switzerland, 2017). 10.1007/978-3-319-41912-1.

Association of acute chest syndrome with plasma levels of thrombospondin-1

Dr. Enrico Novelli, along with Drs. Gladwin, Kato, Ragni and Isenberg, have found an association of acute chest syndrome with plasma levels of thrombospondin-1, a protein that regulates nitric oxide production and blood cell adhesion.

Novelli EM, Kato GJ, Ragni MV, Zhang Y, Hildesheim ME, Nouraie M, Barge S, Meyer MP, Hassett AC, Gordeuk VR, Gladwin MT, Isenberg JS. (2012). Plasma thrombospondin-1 is increased during acute sickle cell vaso-occlusive events and associated with acute chest syndrome, hydroxyurea therapy, and lower hemolytic rates. Am J Hematol. 87(3):326-30. PMID: 22318901. PMCID: PMC3619659. DOI: 10.1002/ajh.2274.