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Am. J. Respir. Cell Mol. Biol., Volume 26, Number 3, March, 2002 333-340

Origin, Differentiation, and Maturation of Human Pulmonary Veins

Susan M. Hall, Alison A. Hislop, and Sheila G. Haworth

Unit of Vascular Biology and Pharmacology, Institute of Child Health, University College, London, United Kingdom

Recent studies on human embryonic and fetal lungs show that the pulmonary arteries form by vasculogenesis. Little is known of the early development of the pulmonary veins. Using immunohistochemical techniques and serial reconstruction, we studied 18 fetal and neonatal lungs. Sections were stained with antibodies specific for endothelium (CD31, von Willebrand factor) and smooth muscle (alpha  and gamma  smooth muscle actin, smooth muscle myosin, calponin, caldesmon, and desmin) and antibodies specific for the matrix glycoprotein tenascin, the receptor protein tyrosine kinase EphB4, and its ligand ephrinB2. Kiel University-raised antibody number 67 (Ki67) expression allowed qualitative assessment of cell replication. By 34 d gestation, there was continuity between the aortic sac, pulmonary arteries, capillaries, pulmonary veins, and atrium. The pulmonary veins formed by vasculogenesis in the mesenchyme surrounding the terminal buds during the pseudoglandular period and probably by angiogenesis in the canalicular and alveolar stages. EphB4 and ephrinB2 did not distinguish between presumptive venous and arterial endothelium as they do in mouse. All venous smooth muscle cells derived directly from the mesenchyme, gradually acquiring smooth muscle specific proteins from 56 d gestation. Thus, both pulmonary arteries and veins arise by vasculogenesis, but the origins of their smooth muscle cells and their cytoskeletal protein content are different.

Abbreviations: alpha smooth muscle specific actin, alpha -SM actin; cluster of differentiation number CD31, CD31; gamma smooth muscle specific actin, gamma -SM actin; Kiel University-raised antibody number 67, Ki67; smooth-muscle-specific myosin heavy chain SM1, SM-1; vascular endothelial growth factor, VEGF.




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