Metabolism of surfactant phosphatidylcholine molecular species in cftrtm1HGU/tm1HGU mice compared to MF-1 mice

Incftr(tm1HGU/tm1HGU) mice an animal model designed to study pathophysiologic alterations due to the CFTR defect founded inctstic fibrosis, surfactant phopholipids of bronchoalveolar lavage fluid (BALF) are increased. To study the metabolical basis of such increases, we intraperitoneally injected cftr(tm1HGU/tm1HGU) mice [methyl-H-3] choline and measured [methyl-H-3]choline incorporation into phosphatidylcholine (PC) molecular species of lung tissue and BALF after 1.5 to 24 hours. MF1 and MF1 x cftr(tm1HGU/1HGU) hybrid mice served as controls. In tissue [methyl-H-3]choline incorporation into total PC was constant for 24 hours and identical in control and cftr(tm1HGU/tm1HGU) mice. However, from 1.5 to 24 hours there was a shift of [methyl-H-3]choline incorporation from palmitoyloleoyl-PC and palmitoyllinoleoyl-PC towards PC species enriched in surfactant, dipalmitoyl-PC, palmitoylmyristoyl-PC, and palmitoylpalmitoleoyl-PC. The relative and absolute H-3-labels of PC species were identified for cftr(tm1HGU/tm1HGU) compared to control mice. In BALF [methyl-H-3]choline of total PC increased from 1.5 to 24 hours (R-2 > .98), mainly due to [methyl-H-3]choline-labelled dipalmitoyl-PC, in all experimental groups. In BALF from cftr(tm1HGU/tm1HGU) mice, the [methyl-H-3]choline label of total PC and individual PC species was significally increased over controlled values after 24 hours, but not after 1.5 to 6 hours. Numbers and compositions of BALF cells were not different between controls and cftr(tm1HGU/tm1HGU) mice. We conclude that increased alveolar phospholipids in cftr(tm1HGU/tm1HGU) mice is likely due to decreased reuptake of surfactant.