Laminins are trimeric glycoprotein components of basement membranes. Each l
aminin has three structurally similar chains, designated alpha, beta, and g
amma. Five laminin alpha chains are now known. In previous studies using mo
noclonal antibody 4C7, laminin al was thought to be present in basement mem
branes of human lung throughout development and in the adult, but recent ex
pression studies have demonstrated that 4C7 identifies laminin alpha5 rathe
r than alpha1. To determine the temporal and spatial patterns of laminin al
pha1 and laminin alpha5 in developing human lung, we prepared complementary
DNA probes specific for laminin alpha1 and alpha5 messenger RNAs (mRNAs).
By Northern analysis, laminin alpha1 mRNA was prominent in first-trimester
fetal lung, but was not detectable at 23 wk or at later times. In contrast,
laminin alpha5 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 alpha5 was persistent from the
early fetal period. In situ hybridization localized laminin al expression t
o distal epithelium in the first-trimester lung, and laminin alpha5 to all
epithelium and developing pulmonary arteries from the first trimester throu
gh the perinatal period. These studies indicate that laminin al expression
is restricted to early human lung morphogenesis, whereas the expression of
laminin alpha5 in human lung is continuous from early lung development thro
ugh adult life. It is evident that laminin alpha1 and laminin alpha5 have d
ifferent roles in the development of the human lung.