This explanation would be consistent with previous studies showing that TLR4 signaling is required for increased expression of leukocyte adhesion molecules in endothelial cells after exposure to CFH (44), for complement-associated damage of the endothelium during hemolysis (45), and for development of acute chest syndrome mediated by nonhematopoietic cells in a murine model of sickle cell disease (42). This evidence concerns the gene TLR4 and sickle cell disease.