The lung undergoes marked alterations during the latter part of gestation in preparation for its transition to a fluid filled state. The most notable and important event is the appearance of the surfactant system. There is evidence that several hormones may be involved in determining the final maturation process. Recent evidence suggests that a fibroblast-pneumocyte factor (FPF) may play a role in amplication of the response of type II cells to cortisol. It is not known how FPF acts upon the type II cell, what other hormones may elicit their effect via FPF, or how universal the FPF may be on different systems of type II cells. The present application will utilize two different systems of culturing fetal type II cells in order to determine the possible interrelationships of FPF, glucocorticoids, T3 and insulin upon surfactant production. One system is a primary monolayer culture containing a greater than 90 percent enrichment in type II cells. The second system contains type II cells in aggregate (organotypic) culture where the cells maintain an in vivo like shape, cell-to-cell contacts, and are stable for several weeks in vitro. These two systems are sufficiently different so as to expect that they may respond to exogenous factors differently. Thus they make an excellent pair of systems to study how universal the effect of FPF is. It will be determined whether FPF augments the response to these cultures to dexamethasone and T3 and whether T3 or insulin affect production of FPF by fibroblasts. By use of several different isotopes, assay of activities of lipid synthesizing enzymes, and measurement of pool sizes of different phosphatidylcholines it will be determined how FPF acts upon the type II cell. A determination of whether FPF affects suriactant secretion or type II cell growth will also be made. A secondary objective of this application is the factor produced by lung fibroblasts which inhibits surfactant synthesis. It will be determined whether insulin or high glucose concentrations affect production of the inhibitors. This is of importance because infants of diabetic mothers have an increased incidence of respiratory distress syndrome. The mechanism by which the inhibitor affects the type II cell will also be studied.
| Visser, M R; Jacob, H S; Goodman, J L et al. (1989) Granulocyte-mediated injury to herpes simplex virus-infected human endothelium. Lab Invest 60:296-304 |
