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Lung disaturated phosphatidylcholine (DSPC) turnover was investigated in normal C57 black and mutant beige mice; the latter have been postulated to have microtubular defects. Turnover experiments were performed on 117 black and 74 beige mice that were assayed for lamellar body-rich fraction (LB) and alveolar lavage fluid (AF) DSPC from 0.5 to 100 h after injection of [3H]glycerol. The data were analyzed by a program that derived the best-fit rate constants for an operator-chosen compartmental model. For black mice, a simple model with bidirectional exchange of DSPC between LB and AF compartments fitted the data almost as well as more complex models. This model yielded a turnover time of 5.9 h, a biological half-life of 16 h, and recycling of AF DSPC into LB of 47%. There was some evidence to suggest that DSPC might be degraded rather than recycled as a unit. For beige mice, the DSPC turnover time was 4.8 h, and its biological half-life was 40 h. The AF DSPC pool was smaller than in black mice, but the LB pool was larger. The bidirectional flux of DSPC between AF and LB was much greater than in black mice, the percent of recycling being 85. These data do not support a microtubular defect in beige mice, but the calculations for beige mice are based on a model of questionable validity.

Mouse alveolar surfactant can be separated by equilibrium centrifugation on continuous sucrose gradients into three subtypes which we call "ultraheavy", "heavy", and "light" on the basis of their buoyant densities. We examined their metabolic relationship by in vivo labeling studies and by physical manipulation, cycling the surface area in vitro in an attempt to convert one subtype into another. Labeling studies indicated rapid quantitative progression of surfactant through ultraheavy, heavy, and light subtypes in sequence. To mimic the in vivo conversion of subtypes in vitro we "cycled" the surface area of surfactant in plastic tubes. Newly secreted surfactant obtained from incubated lungs, as well as surfactant obtained by alveolar lavage and lamellar bodies, exhibited conversion of material from heavier to lighter subtypes. The conversion between subtypes was quantal and was dependent on cycling, temperature, and time. We conclude that the three subtypes are discrete forms of alveolar surfactant that evolve from one into another. Cycling may provide a means to study the mechanisms of their interconversion in vitro.

Surfactant obtained by bronchoalveolar lavage of normal adult mice was separated into subtypes by a one-step centrifugation to equilibrium on continuous sucrose gradients. Mouse surfactant resolved in this way exists in three subtypes with similar phospholipid compositions. A "light" subtype of buoyant density 1.027 +/- 0.012 (SD) g/ml comprises 43 +/- 18% of the total alveolar lavage phospholipid, has little surface activity, and consists exclusively of small unilamellar vesicles. A "heavy" subtype of buoyant density 1.055 +/- 0.016 g/ml comprises 48 +/- 11% of the total, is surface active, and consists of small amounts of tubular myelin among large empty vesicles. A third component, called "ultraheavy," comprises 9 +/- 4% of the total alveolar lavage phospholipid, has a density of 1.072 +/- 0.020 g/ml, is surface active, and consists of large aggregates of tubular myelin associated with lamellar bodylike structures. Labeling studies suggested that the ultraheavy material was labeled first and was of the same density as purified lamellar bodies. These results are consistent with the view that, in mice, surfactant is secreted into the alveolar compartment in an ultraheavy form, which evolves into the heavy and light forms.