Metabolism of surfactant phosphatidylcholine molecular species in cftr(tm1HGU/tm1HGU) mice compared to MF-1 mice

Incftr(tm1HGU/tm1HGU) mice an animal model designed to study pathophysiolog ic alterations due to the CFTR defect founded inctstic fibrosis, surfactant phopholipids of bronchoalveolar lavage fluid (BALF) are increased. To stud y the metabolical basis of such increases, we intraperitoneally injected cf tr(tm1HGU/tm1HGU) mice [methyl-H-3] choline and measured [methyl-H-3]cholin e incorporation into phosphatidylcholine (PC) molecular species of lung tis sue 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 t otal 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 t owards PC species enriched in surfactant, dipalmitoyl-PC, palmitoylmyristoy l-PC, and palmitoylpalmitoleoyl-PC. The relative and absolute H-3-labels of PC species were identified for cftr(tm1HGU/tm1HGU) compared to control mic e. 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 a ll experimental groups. In BALF from cftr(tm1HGU/tm1HGU) mice, the [methyl- H-3]choline label of total PC and individual PC species was significally in creased over controlled values after 24 hours, but not after 1.5 to 6 hours . Numbers and compositions of BALF cells were not different between control s and cftr(tm1HGU/tm1HGU) mice. We conclude that increased alveolar phospho lipids in cftr(tm1HGU/tm1HGU) mice is likely due to decreased reuptake of s urfactant.