Influence of methylprednisolone on mouse alveolar type 2 cell response to acute lung injury

To determine whether corticosteroids influence alveolar type 2 cell events after acute lung injury, we administered 30 mg/kg/day of methylprednisolone (MP) to mice at various times after a single injection of butylated hydroxytoluene (BHT). Tritiated thymidine (³H-T) autoradiographs were used to study type 2 cell proliferation and differentiation. Type 2 cell maturation was evaluated by ultrastructural analysis of lamellar body volume density and area in cells labeled with ³H-T. The BHT damaged type 1 cells and induced proliferation of type 2 cells. Sixty per cent of type 2 cells labeled with ³H-T on Day 3 differentiated into type 1 cells over a 4-day period. Lamellar body area per cell was unchanged. Early administration of MP (days 1 and 2) inhibited type 2 cell proliferation when lung injury was mild; rebound proliferation occurred after its discontinuation. The MP failed to inhibit proliferation when lung injury was severe. Prolonged MP administration (Days 1 to 5) resulted in greater type 2 cell proliferation, lung injury, and mortality. Late MP administration (Days 3 and 4) impaired differentiation of type 2 to type 1 cells and more than doubled lamellar body area per cell of new type 2 cells. Important interactions appear to exist between proliferation, differentiation, and maturation of alveolar type 2 cells suggesting that agents that influence one of these processes may influence all aspects of type 2 cell function.