Growth factor activity in the lung during compensatory growth after pneumonectomy: Evidence of a role for IGF-1

Abstract

Unilateral pneumonectomy in rats causes compensatory growth of the remaining lung. During this growth, there are large increases in the cell numbers and in the rates of collagen and non-collagen protein production. We examined possible mechanisms by which these changes might occur. Assessment of the effect of bronchoalveolar lavage (BAL) fluid on fibroblasts in vitro demonstrated the presence of stimulatory activity for fibroblast replication in control animals. This activity was greatly increased two and six days postpneumonectomy (115 ± 26% and 75 ± 18% above control values, respectively), but had returned to normal by 14 days. Preliminary characterization suggests that the activity is heat labile and consists of at least two moieties with apparent molecular weights of 5-15 kD and 70-220 kD. The activity was partially blocked by antibodies to insulin-like growth factor-1 (IGF-1), and levels of IGF-1 were increased by about 100% (p < 0.001) two days after pneumonectomy compared with control values. Examination of BAL cells demonstrated an early influx of leucocytes into the remaining lung of pneumonectomozed rats. At two days, about 25% of the lavageable cells were neutrophils, but macrophages were the predominant cell type at all times. The extravascular albumin space of the lung increased by about 65% (p < 0.01), six days after pneumonectomy. The influx of circulatory proteins and cells are potential sources of the increased mitogenic activity observed in the lung.