Diversion of the postinjury mesenteric lymph decreased early BM suppression after LC or LC with HS. However, this improved BM function occurred at the expense of impaired lung healing and an increased susceptibility to pulmonary infection. As mobilized BM cells differentiate into pneumocytes, these data indicate that mobilization of BM cells to the site of injury is an adaptive and necessary response for successful wound healing and tissue repair.

Volpe MV, Chung E, Ulm JP, Gilchrist BF, Ralston S, Wang KT, Nielsen HC. Aberrant cell adhesion molecule expression in human bronchopulmonary sequestration and congenital cystic adenomatoid malformation. Am J Physiol Lung Cell Mol Physiol 297: L143-L152, 2009. First published May 1, 2009 doi:10.1152/ajplung.90618.2008.-In many organs, integrins and cadherins are partly regulated by Hox genes, but their interactions in airway morphogenesis and congenital lung diseases are unknown. We previously showed that the Hox protein HoxB5 is abnormally increased in bronchopulmonary sequestration (BPS) and congenital cystic adenomatoid malformation (CCAM), congenital lung lesions with abnormal airway branching. We now report on ␣ 2-, ␣3-, and ␤1-integrin and E-cadherin expression in normal human lung and in BPS and CCAM tissue previously shown to have abnormal HoxB5 expression and on the relationship of cell adhesion molecule expression to Hoxb5 regulation. ␣ 2-, ␣3-, and ␤ 1 -integrins and E-cadherin expression in normal human lung and BPS and CCAM were evaluated using Western blot and immunohistochemistry. Fetal mouse lung fibroblasts with Hoxb5-specific siRNA downregulation were evaluated for ␣ 2-integrin protein levels by Western blot. Compared with normal human lung, a previously undetected ␣ 2-integrin isoform potentially lacking essential cytoplasmic sequences was significantly increased in BPS and CCAM, and ␣ 2-integrin spatial and cellular expression was more intense. Ecadherin protein levels were also significantly increased, whereas ␣ 3 increased in CCAM compared with canalicular, but not with alveolar, stage lung. ␤ 1-integrin levels were unchanged. We conclude that in BPS and CCAM, altered ␣ 2-integrin cytoplasmic signaling contributes to abnormal cellular behavior in these lung lesions. Aberrant cell adhesion molecule and Hox protein regulation are likely part of the mechanism involved in the development of BPS and CCAM.