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In order to define the origin and fate of lipid-filled interstitial cells (LIC) in the neonatal rat lung, 4- and 11-day-old rats were injected with tritiated thymidine (3H-T) and killed 1 to 96 h later. Thymidine-labeled lung cells were identified in autoradiographs and analyzed ultrastructurally. Interstitial cells accounted for 61% of 3H-T-labeled cells at 4 days but only 26% at 11 days. The LIC had a different labeling index than did nonlipid interstitial fibroblasts (NLIC) at each age, and also had distinct morphologic characteristics. At no time point did labeled LIC lose their lipid and become NLIC or vice versa. These results suggest that at least 2 separate populations of interstitial fibroblasts exist in the neonatal rat lung, probably with distinct functions. This supports the concept of tissue fibroblast heterogeneity.

To study the relation between normal and abnormal alveolar type 2 cells and lung repair after injury, and to gain insight into the defect responsible for the giant lamellar bodies in type 2 cells of the beige mouse (an animal model of the Chediak-Higashi syndrome), we produced lung injury with a single injection of butylated hydroxytoluene (BHT). Type 2 cell proliferation and differentiation were analyzed in light microscopic autoradiographs of mice that had received tritiated thymidine (3H-T) at intervals after the injection of BHT. The approximate age of 3H-T labeled type 2 cells and lamellar body volume density and area were correlated by combining light microscopic autoradiography with ultrastructural morphometry. Type 2 cell proliferation and differentiation were identical in normal and in beige mice. In normal mice, the lamellar body area per cell was unchanged at the time periods studied. In beige mice, the lamellar body area per cell, which was initially 9 times that of the normal mice, decreased to nearly normal values after mitosis, and then increased over the subsequent 7 days of study. Thus, the abnormal type 2 cell of the beige mouse was able to proliferate and differentiate in a normal fashion after lung injury. The beige mouse defect, which results in impaired lamellar body release, was transiently corrected in the perimitotic period. The postmitotic enlargement of lamellar bodies provided a model for studying the basic defect in the Chediak-Higashi syndrome and the process of type 2 cell maturation.

We have previously shown that alveoli of neonatal rat lungs contain 2 morphologically distinct fibroblasts; 1 that contains lipid droplets and 1 that does not. We have named these lipid interstitial cells (LIC) and nonlipid interstitial cells (NLIC). In this study, using stereologic methods, we evaluated the distribution of LIC and NLIC in the alveoli of immature and mature rats, hamsters, and mice and quantitated cytoplasmic lipid in the LIC. We found that fibroblasts account for approximately 50% of resident alveolar wall cells in immature and 20% in mature rodent lungs. At each age LIC accounted for half of the fibroblasts. There were age and species differences in the amount of LIC lipid. The volume density of cytoplasmic lipid was higher in immature rats (0.285) than in mice (0.205) or hamsters (0.010) and was higher in mature mice (0.176) than in hamsters (0.051) or rats (0.019). Possible explanations for these differences are discussed. Bundles of characteristic cytoplasmic myofilaments established that the LIC was identical to the previously described contractile interstitial cell of the lung. These studies confirm the presence of 2 distinct fibroblasts in the alveoli of immature and mature rodents of several species.