A PUTATIVE SUB-10-KDA BASEMENT-MEMBRANE ACTIVITY REQUIRED FOR LUNG ALVEOLAR FORMATION IN-VITRO

Basement membrane promotes the reassembly of isolated type II alveolar cells into alveoli-like structures, a process attributable in part to a novel cell adhesion site in the al-chain of laminin-1 (M. L. Matter and G. W. Laurie. J. Cell Biol. 124: 1083-1090, 1994). The possibilit y that basement membrane contains other alveolarization activities was probed by subtraction analysis and use of neutralizing antibodies. De letion of components <100 kDa, and subsequently <10 kDa, reduced alveo lar cross-sectional area by 70% to 22-25 x 10(3) mu m(2): the approxim ate size of alveolar-like structures formed on purified laminin-1 alon e. The deleted basement membrane material was adhesive for type II alv eolar cells but failed to support alveolar formation in the absence of laminin-1. Preincubation of basement membrane with neutralizing anti- epidermal growth factor (EGF), -basic fibroblast growth factor (bFGF) -insulin-like growth factor (IGF)II, or -transforming growth factor (T GF)-beta antibodies bad no inhibitory effect; Because both subtracted basement membrane preparations have in common the exclusion of compone nts <10 kDa, these results are interpreted as pointing to a sub-10-kDa alveolarization activity(s) that plays a key accessory role in lamini n-1-dependent alveolar formation.