EMAP II: a modulator of neovascularization in the developing lung

Neovascularization is a key regulatory process in fetal growth and developm ent. Although factors promoting growth and development of the pulmonary vas culature have been investigated, nothing is known regarding the molecular m echanisms that may counteract these stimuli. Endothelial monocyte-activatin g polypeptide (EMAP) II has recently been identified as an antiangiogenic f actor in tumor vascular development. We postulated that EMAP II is a putati ve negative modulator of lung vascular growth. EMAP II mRNA and protein dec rease fivefold (P < 0.01) as the developing lungs in the fetal mouse progre ss from having poor vascularization (day 14) to having complete vascular de velopment at term (day 18.5). EMAP II protein expression continues to remai n low throughout postnatal life and into adulthood, with the exception of a surge that correlates with microvascular maturation Furthermore, through t he use of in situ hybridization and immunohistochemistry, EMAP II is locali zed throughout the lung, with significant expression in the submyoepithelia l area during the early stages of lung development when there is minimal va scular development. In contrast, EMAP II is distributed around the large ve ssels during the end of vascular development, suggesting that EMAP II modul ates the neovascularization process. We speculate that EMAP II is a directo r of neovascularization in the developing lung.