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Am. J. Respir. Cell Mol. Biol., Volume 23, Number 6, December, 2000 742-747

Expression Patterns of Laminin alpha 1 and alpha 5 in Human Lung during Development

Richard A. Pierce, Gail L. Griffin, Jeffrey H. Miner, and Robert M. Senior

Divisions of Pulmonary and Critical Care Medicine and Renal Diseases, Department of Medicine, and the Department of Cell Biology and Physiology, Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri

Laminins are trimeric glycoprotein components of basement membranes. Each laminin has three structurally similar chains, designated alpha , beta , and gamma . Five laminin alpha  chains are now known. In previous studies using monoclonal antibody 4C7, laminin alpha 1 was thought to be present in basement membranes of human lung throughout development and in the adult, but recent expression studies have demonstrated that 4C7 identifies laminin alpha 5 rather than alpha 1. To determine the temporal and spatial patterns of laminin alpha 1 and laminin alpha 5 in developing human lung, we prepared complementary DNA probes specific for laminin alpha 1 and alpha 5 messenger RNAs (mRNAs). By Northern analysis, laminin alpha 1 mRNA was prominent in first-trimester fetal lung, but was not detectable at 23 wk or at later times. In contrast, laminin alpha 5 mRNA was readily detected in early fetal lung and remained present thereafter. Immunohistochemical staining demonstrated laminin alpha 1 only in early fetal lung, whereas laminin alpha 5 was persistent from the early fetal period. In situ hybridization localized laminin alpha 1 expression to distal epithelium in the first-trimester lung, and laminin alpha 5 to all epithelium and developing pulmonary arteries from the first trimester through the perinatal period. These studies indicate that laminin alpha 1 expression is restricted to early human lung morphogenesis, whereas the expression of laminin alpha 5 in human lung is continuous from early lung development through adult life. It is evident that laminin alpha 1 and laminin alpha 5 have different roles in the development of the human lung.




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