Back to Search
Start Over
Comparison of the morphological and biochemical changes in normal human lung fibroblasts and fibroblasts derived from lungs of patients with idiopathic pulmonary fibrosis during FasL-induced apoptosis
- Source :
- The Journal of Pathology. 202:486-495
- Publication Year :
- 2004
- Publisher :
- Wiley, 2004.
-
Abstract
- It is increasingly recognized that the morphological changes of apoptosis vary between cell types. This heterogeneity reflects the wide range of cellular proteins and enzymes involved in apoptotic pathways. Fibroblast apoptosis is crucial to the regression of scars and the restitution of healthy tissue during wound repair and may be aberrant in diseases such as idiopathic pulmonary fibrosis (IPF). The biochemical and morphological changes characterizing fibroblast apoptosis are unknown and may provide insights into the specific enzymatic mediators activated in these cells. This study aimed to examine the morphological changes of fibroblast apoptosis in both primary normal lung fibroblasts (normal-Fb) and fibroblasts obtained from patients with idiopathic pulmonary fibrosis (IPF-Fb) and to correlate these changes with conventional biochemical markers. Transmission electron microscopy (TEM) and video time-lapse microscopy demonstrated no difference in the duration of fibroblast apoptosis in response to FasL (6 +/- 0.3 h in normal-Fb and 6.4 +/- 0.2 h in IPF-Fb). However, IPF-Fb were more resistant to FasL-induced apoptosis compared with normal-Fb. Although the majority of morphological changes of normal-Fb and IPF-Fb were similar, the formation of filopodia and condensation of the cytoskeletal bundles in IPF-Fb, and more prominent vacuolation in normal-Fb, were the significant differences between these cell subtypes. Loss of the mitochondrial membrane potential occurred prior to caspase-3 activation, while phosphatidylserine expression, cytokeratin-18 cleavage, and DNA fragmentation commenced after caspase-3 activation. These observations not only suggest that specific enzymatic effectors may be preferentially activated during fibroblast apoptosis, but also provide potential insights into the pathogenesis of IPF.
- Subjects :
- Programmed cell death
Pathology
medicine.medical_specialty
Fas Ligand Protein
Pulmonary Fibrosis
Apoptosis
DNA Fragmentation
Biology
Fas ligand
Pathology and Forensic Medicine
chemistry.chemical_compound
Idiopathic pulmonary fibrosis
Fibrosis
Pulmonary fibrosis
medicine
Humans
Fibroblast
Lung
Cells, Cultured
Membrane Glycoproteins
Microscopy, Video
Caspase 3
Cell Membrane
Phosphatidylserine
Fibroblasts
medicine.disease
Microscopy, Electron
medicine.anatomical_structure
chemistry
Caspases
Vacuoles
Cancer research
Subjects
Details
- ISSN :
- 10969896 and 00223417
- Volume :
- 202
- Database :
- OpenAIRE
- Journal :
- The Journal of Pathology
- Accession number :
- edsair.doi.dedup.....ea2041e958f5b655d0d22658bb6d17dd