ABSTRACT
The MRP (multidrug resistance-associated protein) transmembrane transporter, which actively transports a wide variety of lipophilic substrates out of cancer cells, has been suggested to play a major role in cell detoxification via efflux of glutathione conjugates. Because bronchial epithelial cells are constantly exposed to environmental pollutants, MRP might be a particularly important defense mechanism against xenobiotics. This study was therefore designed to investigate MRP localization by immunohistochemistry in bronchial epithelial cells collected by scraping from surgical specimens. In parallel, MRP mRNA was detected by reverse transcriptase chain reaction (rt-PCR) in bronchial cell lysates. However, the pattern of protein expression differed markedly according to cell type. In ciliated epithelial cells, immunostaining was restricted to the basolateral surface, without any labeling at the apical surface, which is at variance with the localization of CFTR and MDR1 proteins, other members of the same family of transporters. In basal cells, MRP was present over the entire circumference of the plasma membrane. Basal cells were identified by their morphology and specifically after incubation with an anticytokeratin 17 monoclonal antibody. In conclusion, the different patterns of localization suggest specific roles for MRP in basal and ciliated cells.
Subject(s)
ATP-Binding Cassette Transporters/metabolism , Bronchi/metabolism , Bronchi/cytology , Cilia/metabolism , Drug Resistance, Multiple/physiology , Epithelium/metabolism , Female , Humans , Immunohistochemistry , Keratins/metabolism , Male , Multidrug Resistance-Associated Proteins , Polymerase Chain Reaction , Transcription, GeneticABSTRACT
The present study analyzes the kinetics of the in vivo degradation of hydrophilic Mitrathane in the peritoneal cavity of mice over a period ranging from 1 to 180 days. The mechanical milling of the polyurethane films produced regularly flattened fragments that in vivo spontaneously oriented into piles. The morphological observations and analysis with the aid of an image analysis system demonstrated that after seven days of swelling the polymer fragments undergo a continuous degradation that leads to an irregular thinning and phagocytosis of the smaller fragments by macrophages with very little chronic inflammation response from surrounding tissues.
Subject(s)
Biocompatible Materials/chemistry , Polyurethanes/chemistry , Animals , Biodegradation, Environmental , Female , Image Processing, Computer-Assisted , Kinetics , Macrophages, Peritoneal/physiology , Mice , Mice, Inbred Strains , Particle Size , Peritoneal Cavity , Phagocytosis , Porosity , Prostheses and ImplantsABSTRACT
This paper presents an original experimental procedure designed to evaluate, by a two step in vivo/in vitro combination, the long-term biocompatibility of synthetic materials developed for clinical applications. The efficacy of the test is illustrated by the experimental results obtained with various materials currently used in medicine (Dacron, RCH) and also with three recently synthesized compounds. In the first step of the procedure, the sample was grafted for at least 5 months in the peritoneal cavity of mice, allowing the possible development of delayed sensitization. In the second step, this sensitization was detected by an in vitro test, the Lymphoblastic Transformation Test (LTT), adapted for this new purpose. On the basis of this experiment, the 5 polymers tested were classified into 2 groups: one group did not significantly differ from the control, and the other had a significantly higher incidence of sensitization. As these results were in agreement with the known biocompatibility of these polymers, they demonstrate the validity of the test to classify new polymers.