Lung surfactant comprises mainly phosphatidylcholine (PC) species together with phosphatidylglycerols and surfactant proteins (SP) SP-A to -D. Changes in the concentrations of its principal components dipalmitoyl-PC, palmitoylmyristoyl-PC, palmitoylpalmitoleoyl-PC relative to developmental, structural and physiological differences are only partially understood. Particularly, their attribution to differences in air-liquid interface curvature, compared with dynamic parameters, such as respiratory rate, are controversial. We postulated that during alveolarization the changes in these principal PC components of surfactant differ from those in other phospholipid parameters, and that across endothermic vertebrates their concentrations are related to lung physiology rather than structure. We therefore investigated in rats from postnatal day (d)1 to d42 the pattern of surfactant phospholipids relative to alveolarization (d4-d14), and we discuss these changes in terms of molecular adaptation to pulmonary structure or physiology. Contrary to mammals with advanced alveolarization and increased respiratory rate (RR) at term, concentrations of dipalmitoyl-PC (49-52%) and palmitoylmyristoyl-PC (7-9%) in lung lavage fluid were identical at d1 and d42. At d7-d14, when in rats RR is increased, palmitoyl-myristoyl-PC transiently increased by 2.5- to 3.9-fold at the expense of dipalmitoyl-PC (-32% to 34%) and palmitoyl-palmitoleoyl-PC (-16%). Other lipidomic changes followed essentially different patterns of increase or decrease. Palmitoyl-myristoyl-PC was increased in large aggregates suggesting that it is an integral component of active surfactant. In the overall context of vertebrates, irrespective of age and lung structure, fractions of palmitoyl-myristoyl-PC, dipalmitoyl-PC and palmitoyl-palmitoleoyl-PC correlate with differences in RR rather than alveolar curvature. In adult mammals, however, only concentrations of palmitoyl-palmitoleoyl-PC correlate with RR.

Reduced airway inflammation in CD26-deficient F344 rats appear to be mediated by differences in the recruitment and activity of Tregs. This altered inflammation is associated with differences in the SP expression as well as function.

Human endometrial fibroblasts have been immortalized by infection with simian virus 40 large T antigen and established as a permanent cell line, St-2. Biochemical differentiation of this cell line has been demonstrated by the ability of a decidualizing stimulus, 8-bromo-cAMP plus medroxyprogesterone acetate (MPA), to induce PRL secretion and increase the enzymatic activity of estrone sulfatase. MPA, alone or in combination with estradiol, was unable to elicit this response, but potentiated the effect of 8-bromo-cAMP on PRL production and estrone sulfatase activity. The increase in PRL protein was accompanied by an increase in PRL messenger RNA and increased expression of the insulin-like growth factor-binding protein-1 messenger RNA. The St-2 cell PRL transcript was larger than the pituitary PRL transcript, suggesting its initiation from the distal, nonpituitary, PRL promoter. This was confirmed by reverse transcription-PCR analysis of PRL transcripts using primers specific for the additional sequences present only in the 5'-untranslated region of RNA initiated from the distal promoter. Transient transfection of a reporter construct containing 3000 bp of DNA 5' to the decidual-specific promoter of the human PRL gene demonstrated that cAMP was capable of activating this distal promoter in St-2 cells. In conclusion, this novel cell line provides an interesting new model in which to pursue aspects of biochemical differentiation of human endometrium in vitro.

Summary The use of lungs from donation after cardiac death (DCD) donors is one of the strategies to increase the donor pool. The aim of this study was to assess the surfactant alterations in DCD donor lungs. Pigs were sacrificed and left untouched for 1 (DCD1), 2 (DCD2) and 3 (DCD3) h. Lungs were then topically cooled with saline for 1, 2 or 3 h to reach a total ischemic time of 4 h. Heart‐beating donors (HBD) served as control group. Bronchoalveolar lavage (BAL) samples were assessed for protein levels and surfactant function. Left lungs were prepared for ex‐vivo evaluation. Pulmonary vascular resistance (PVR), oxygenation, airway pressure (AWP) and wet‐to‐dry weight ratio were significantly different between HBD and DCD3 groups (P < 0.05). BAL protein levels were statistically higher in DCD3 compared with HBD group (P < 0.05). Surface tension and surface tension measured at minimal bubble diameter (adsorption) were lower in HBD compared with DCD groups (P < 0.05). Adsorption was also lower in DCD1 compared with DCD2 (P < 0.05). Adsorption and surface tension were correlated with oxygenation and AWP (P < 0.05). This study has shown that lung function deteriorates with increasing warm ischemic time intervals. BAL protein, surface tension, adsorption, peak AWP and PVR increase significantly after 2 h of warm ischemia together with a significant reduction of the ratio PaO2/FiO2.

Surfactant comprises phosphatidylcholine (PC) together with anionic phospholipids, neutral lipids, and surfactant proteins SP-A to-D. Its composition is highly specific, with dipalmitoyl-PC, palmitoyl-myristoyl-PC, and palmitoyl-palmitoleoyl-PC as its predominant PC species, but with low polyunsaturated phospholipids. Changes in pulmonary metabolism and function in response to injuries depend on their duration and whether adaptation can occur. We examined in rats prolonged (7 days) versus acute (2 days) exposure to non-lethal oxygen concentrations (85%) with respect to the composition and metabolism of individual lung phospholipid molecular species. Progressive inflammation, structural alteration, and involvement of type II pneumocytes were confirmed by augmented bromodeoxyuridine incorporation, broadening of alveolar septa, and increased granulocyte, macrophage, SP-A, and SP-D concentrations. Surfactant function was impaired after 2 days, but normalized with duration of hyperoxia, which was attributable to inhibition but not to alteration in SP-B/C concentrations. Phospholipid pool sizes and PC synthesis by lung tissue, as assessed by [methyl-(3)H]-choline incorporation, were unchanged after 2 days, although after 7 days they were elevated 1.7-fold. By contrast, incorporation of labeled PC into tissue pools of surfactant and lung lavage fluid decreased progressively. Moreover, concentrations of arachidonic acid containing phospholipids were augmented at the expense of saturated palmitoyl-myristoyl-PC and dipalmitoyl-PC. We conclude a persisting impairment in the intracellular trafficking and secretion of newly synthesized PC, accompanied by a progressive increase in alveolar arachidonic acid containing phospholipids in spite of recovery of acutely impaired surfactant function and adaptive increase of overall PC synthesis.