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 afer 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.
D000208:Acute Disease; D000818:Animals; D001345:Autoradiography; D002084:Butylated Hydroxytoluene; D002455:Cell Division / Q000187:drug effects; D005260:Female; D008171:Lung Diseases / Q000139:chemically induced / Q000473:pathology*; D008775:Methylprednisolone / Q000494:pharmacology*; D051379:Mice; D011650:Pulmonary Alveoli / Q000187:drug effects*
D002084:Butylated Hydroxytoluene; D008775:Methylprednisolone