CFTR, MDR1, and MRP1 Immunolocalization in Normal Human Nasal Respiratory Mucosa

Abstract

CFTR (cystic fibrosis transmembrane conductance regulator), MDR1 (multidrug resistance), and MRP1 (multidrug resistance-associated protein), members of the ABC transporter superfamily, possess multiple functions, particularly Cl(-), anion, and glutathione conjugate transport and cell detoxification. They are also hypothesized to have a number of complementary functions. It is generally accepted that data obtained from nasal mucosa can be extrapolated to lower airway cell physiology. The aim of the present study was to investigate by immunohistochemistry the differential localization of CFTR, MDR1, and MRP1 in the normal mucosa of 10 human nasal turbinates. In ciliated epithelial cells, CFTR was inconstantly expressed at the apical cell surface, intense membranous labeling was observed for MDR1, and intense cytoplasmic labeling was observed for MRP1. In the glands, a higher level of expression was observed on serous cells, at the apical surface (for CFTR), on lateral membranes (for MDR1), and with an intracytoplasmic distribution (for MRP1). In conclusion, CFTR, MDR1 and MRP1 are expressed in the epithelium and glands of the nasal respiratory mucosa, but with different patterns of expression. These results suggest major roles for CFTR, MDR1, and MRP1 in serous glandular cells and a protective function for MDR1 and MRP1 in respiratory ciliated cells. (J Histochem Cytochem 48:1215-1222, 2000)

Portrait of multifaceted transporter, the multidrug resistance-associated protein 1 (MRP1/ABCC1)

“…Initial reports suggested apical localization [146]; however, more recent studies revealed that this transporter localizes to the basolateral membrane of syncytiotrophoblasts [104,147]. In addition to the plasma membrane localization, intracellular expression of MRP1 has been found in various cell lines [3,24,44,128,167] and normal tissue samples [42,174]. The subcellular organelles where MRP1 accumulation was seen include endocytic vesicles [3], perinuclearly located lysosomes [128], and trans-Golgi vesicles [44,167].…”

“…Because these studies were performed with cells overexpressing the transporter and/or with MRP1 tagged with fluorescent proteins, for the evaluation of the physiological relevance of these observations, it should be considered that either overexpression or tagging may greatly influence the subcellular localization pattern. However, the predominant cytoplasmic expression of MRP1 seen in several normal tissues [42,174] indicates that the intracellular localization of the transporter might have a physiological role. The interesting finding that MRP1 rapidly translocates from the Golgi to the plasma membrane in response to unconjugated bilirubin exposure [44] suggests that intracellularly expressed MRP1 serves as a cellular reservoir, which can be easily mobilized and targeted to the site of action.…”

Detection of a large heterozygous deletion and a splicing defect in the CFTR transcripts from nasal swab of a Japanese case of cystic fibrosis

“…CFTR immunoreactivity was found in the apical membrane of ciliated epithelial cells and serous glandular cells of human nasal turbinates. 23 Nasal epithelial cells can be non-invasively and repeatedly obtained using a swab. Recent progress on reversetranscriptase PCR allows amplification of mRNA starting with a low copy number.…”

MDR1 gene polymorphisms and P-glycoprotein expression in respiratory diseases

“…Epithelial cells of the trachea and major bronchi stained strongly for P-gp while staining of the smaller bronchi is patchy or absent. P-gp was also found in the lateral membranes of normal nasal respiratory mucosa 19 . In human and rat type I epithelium, P-gp is located at the luminal side whereas freshly isolated type II cells lack P-gp 20 .…”