Published ahead of print on December 12, 2003, doi:10.1165/rcmb.2003-0145OC
© 2004 American Thoracic Society DOI: 10.1165/rcmb.2003-0145OC Epithelial–Mesenchymal Interactions Are Linked to NeovascularizationDepartments of Pediatrics, Cardiothoracic Surgical Research and Surgery, Childrens Hospital Los Angeles Research Institute, Los Angeles; Center for Craniofacial Molecular Biology, and University of Southern California Keck School of Medicine and School of Dentistry, Los Angeles, California; and Departments of Surgery and Pediatrics, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, New Jersey Address correspondence to: Dr. Margaret Schwarz, UMDNJ-Robert Wood Johnson Medical School, 125 Paterson Street, CAB 7036, New Brunswick, NJ 08903. E-mail: m.schwarz{at}umdnj.edu Lung morphogenesis is dependent on interactions between mesenchymal and epithelial cells. We have previously demonstrated that inhibition of neovascularization by endothelial monocyte–activating polypeptide (EMAP) II also attenuates fetal lung morphogenesis in vivo, and hypothesized that epithelial–mesenchymal interactions are regulated by vascular signals. To address this postulate, we evaluated the formation of epithelial cysts in vitro and assessed this complex interaction through: (i) identification of vascular formation in vitro; (ii) assessment of the effect of selective vascular inhibition on cell viability, proliferation, and cellular interactions as measured by epithelial cyst formation; and (iii) examination of whether there is an interdependent relationship between epithelial and mesenchymal cells and a vascular mediator's protein expression. Vascular networks in vitro formed in direct relationship to the presence of epithelial cysts. Disruption of the vasculature by delivery of a selective antiangiogenic protein EMAP II was associated with disruption of epithelial cyst formation. Lastly, control of the vascular formation regulatory protein EMAP II is a direct result of epithelial–mesenchymal cell interactions. These findings suggest that vascular formation modulates and is modulated by the normal cellular communication and interactions that direct lung morphology.
Abbreviations: endothelial-monocyte–activating polypeptide, EMAP • mature 21-kD form of EMAP, mEMAP II • phosphate-buffered saline, PBS This article has been cited by other articles:
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