Browsing by Author "Tschernig, T."

We tested the hypothesis whether allergic airway inflammation in ovalbumin sensitized and challenged Brown Norway rats is associated with intrinsic surfactant alteration and dysfunction. The determination of intra-alveolar surfactant subtypes and alveolar edema within their original microenvironment is only possible using an ultrastructural stereological approach. Therefore both lungs of control and asthmatic rats were fixed by vascular perfusion. The volume fractions of surfactant subtypes and the epithelial surface fraction covered with alveolar edema were determined by point and intersection counting. Furthermore, lung resistance was measured by means of whole-body plethysmography. The surface activity of surfactant from bronchoalveolar lavage was determined as minimum surface tension at minimal bubble size with a pulsating bubble surfactometer. Compared with controls, in asthmatics (1) the fraction of inactive unilamellar forms was significantly increased from 56% to 66%, (2) the fraction of alveolar epithelium covered with alveolar edema visible by light microscopy was significantly increased from 0.7% to 5.0%, (3) the fraction of alveolar epithelium covered with fluid seen by electron microscopy expanded significantly from 5% to 21%, (4) lung resistance was significantly elevated from 14% to 86% and (5) surface tension was enhanced from 6 mN/m to 12 mN/m. Thus, the inflammatory process after allergen challenge of sensitized Brown Norway rats causes intra-alveolar surfactant alterations. These surfactant alterations might contribute to small airway dysfunction.

Keratinocyte growth factor (KGF) induces transient proliferation of alveolar type II cells (AEII) associated with surfactant alterations. To test the hypothesis that homeostasis of intracellular phospholipid stores is maintained under KGF-induced hyperplasia, we (1) collected tissue from adult rat lungs, fixed for light and electron microscopy 3 days after intratracheal instillation of 5 mg recombinant human (rHu) KGF/k9 body weight or phosphate-buffered saline (PBS), and from untreated control animals (five animals/group) for design-based stereology of AEII and lamellar body (LB) ultrastructure; and (2) we analyzed uptake and distribution of instilled radiolabeled phospholipids. After rHuKGF, AEII-coverage of alveolar walls (PBS:8.3 +/- 3.0%; rHuKGF:30.6 +/- 4.8%) and number of AEII/ ml lung volume (PBS:28.5 +/- 6.5 x 10(6), rHuKGF:48.2 +/- 5.8 x 10(6)) were increased (p < 0.008). Number (PBS:97 +/- 25; rHuKGF:54 +/- 7) and volume (PBS:45.3 +/- 13.8 mum(3); rHuKGF:21.0 +/- 4.7 mum(3)) of LBs per cell were decreased (p < 0.008), but not total amount/ml lung volume (PBS:128 +/- 46. 4 x 10(7) mum(3); rHuKGF:103 +/- 34.7 x 10(7) mum(3)). This was paralleled by a shift to larger LBs. After rHuKGF, radiolabeled phospholipids accumulated in whole lung tissue relative to lavage fluid (p < 0.01). However, less radiolabel was incorporated per cell (p < 0.01). We conclude that under rHuKGF-induced AEII proliferation intracellular surfactant was decreased per single cell, whereas a constant amount was maintained per unit lung volume. We suggest that surfactant homeostasis is regulated at the level of phospholipid transport processes, for example, secretion and reuptake.

Growth factors may be involved in sudden infant death (SID). Among these factors, the insulin-like growth factor (IGF) family is important in human fetal and perinatal organ growth and development. In order to detect probable differences in the occurrence and distribution of components of the ICF system, tissue samples from liver, lung, skin, parotid and thyroid gland, gut and cerebellum from SID children (n=9) and controls (n=6) aged between 14 and 258 days of life (mean 105 days) were stained immunohistochemically using antibodies against IGF-I, IGF-II and their specific IGF-I-receptor (IGF-IR). In contrast to controls in hepatocytes of SLD children a reduction or an absence of immunoreactivity for IGF-I and IGF-IR and a weaker staining for IGF-II was detected. IGF-II in smooth muscle layers in the gut and IGF-I in epithelial cells in intestinal specimens also showed a reduced immunoreactivity in SID children and those who died traumatic deaths. In the other organs examined no significant differences in the. distribution of the insulin-like growth factor system between the groups could be detected, indicating that in SID children no fundamental differences or alterations in the physiology of the IGF system occur. Because of the decreased immunostaining of IGFs in the liver and intestine of SLD cases, a local dysregulation may be discussed. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.