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A4632 - Structural and Functional Changes of Alveolar Type II Cells with Age and Acute Lung Injury
Author Block: C. Brandenberger, C. C. von Ziegner, C. Mühlfeld; Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.
RATIONALE: With advancing age, the lung becomes more susceptible to injury. As progenitor cells of the alveolar epithelium and producers of surface tension lowering surfactant, alveolar type II (ATII) cells have a crucial function in lung injury and repair. However, very little is known about changes ATII cells undergo with aging and how this affects the response to acute lung injury (ALI). Here, we tested the hypothesis that structural ATII cell characteristics, surfactant protein expression and senescence differs between young (12 week) and old (18 month) mice with ALI. METHODS: ALI was induced by intranasal application of 2.5 mg lipopolysaccharide/kg BW (n = 10) or saline for control animals (n = 7). The lungs were excised 24 h later and embedded for histopathology and stereological analysis or frozen and later processed for western blot and gene expression analysis. Using stereology, the number and volume of ATII cells, as well as their ultra-structural composition, including surfactant storing lamellar bodies, were estimated. Additionally, the expression of surfactant proteins and senescence markers was analyzed. RESULTS: Pulmonary histopathology revealed a greater injury with more neutrophilic influx and enhanced edema formation in old mice. The expression of stress-associated senescence marker p16 was significantly upregulated with ALI in both age groups, but more pronounced in old mice. The number of ATII cells was higher in old than in young mice despite lower cell density. With ALI, the number of ATII cells significantly declined by 26% in old mice, but did not change in young animals. Ultra-structural quantification indicated no alterations in volume fraction of lamellar bodies with age or ALI, however, the mean size of lamellar bodies (volume-weighted mean volume) was 1.8-fold increased in young animals with ALI. Gene expression of surfactant proteins (SP-A, B, C, D) was, with or without injury, significantly lower in lungs of old compared with young mice. While SP-A and SP-D were elevated after injury, SP-C and SP-B were reduced. CONCLUSION: The results of the current study give evidence that the numerical density of ATII cells declines with age and so does the expression of surfactant proteins. ATII cells of old lungs are more susceptible to injury and the morphology of lamellar bodies in ALI differs from younger subjects. These findings support the hypothesis that ATII cell function is impaired with advancing age and thereby contribute to the worse pathology of ALI and impaired regeneration after injury in elderly individuals.