Expression patterns of adhesion receptors in the developing mouse lung: functional implications

A detailed, immunohistological study of mouse lung development from the first appearance of primary lung buds off the laryngo tracheal groove through the formation of the mature, adult lung has been carried out using monoclonal antibodies specific for endothelial cells, smooth muscle cells, adhesion receptors and markers of mature endothelial cell function. These included mAbs specific for PECAM-1, alpha-smooth muscle actin, ICAM-1, ICAM-2, VCAM-1, alpha 4 and alpha 6 integrin subunits, thrombomodulin and factor VIII. The results document a dynamic pattern of receptor expression and indicate that the expansion of the pulmonary vascular system may take place by both angiogenic and vasculogenic processes. They further document differences in receptor expression by vascular and airway smooth muscle. ICAM-1 expression was primarily extravascular during development. The expression patterns of alpha 4 integrin and its counter receptor VCAM-1 lacked the complementarity that might be expected if they were functioning as a receptor/counter-receptor pair in lung development. Thrombomodulin expression patterns support a major role for the thrombin/ thrombomodulin system in lung development. The expression of thrombomodulin only at sites of airway branching suggests that the thrombin/thrombomodulin system could play a pivotal, regulatory role in branching morphogenesis.