The manuscript adds to the growing body of evidence that the innate immune system contributes to non-infectious lung injury and proposes a completely new role for toll-like receptor 4 (TLR4) – regulation of acute microvascular endothelial cell permeability. Because of phenotypic similarity to many other types of acute lung injury, the Egan lab's findings have far-reaching implications. The research provides evidence that functional TLR4 on pulmonary parenchymal cells is responsible for very early and profound pulmonary edema following lung ischemia and reperfusion.
Dr. Egan’s research has focused for many years on lung ischemia-reperfusion injury (IRI), particularly as it relates to the possibility of lung retrieval after an interval of warm ischemia for possible transplant from cadavers, or non-heart-beating donors (NHBDs). If this became widely practical, it could eliminate the critical shortage of lungs for transplant.
The first author of the article, Giorgio Zanotti, MD, was a visiting research scholar in Dr. Egan's lab from the University of Pavia, Italy. He is now a surgery resident at Duke University. The other authors were Monica Casiraghi, MD; John B. Abano, MD; Jason Tatreau, BS (now a UNC medical student); Mayura Sevala, PhD; Hilary Berlin, BS; Susan Smyth, MD, PhD; William Funkhouser, MD; Keith Burridge, PhD; Scott Randell, PhD; and Dr. Egan.
Zanotti G, Casiraghi M, Abano JB, Tatreau JR, Sevala M, Berlin H, Smyth S, Funkhouser WK, Burridge K, Randell SH, Egan TM. Novel critical role of toll-like receptor 4 in lung ischemia-reperfusion injury and edema. Am J Physiol Lung Cell Mol Physiol 2009; 297(1):L52-63.