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Resistance of multidrug-resistant lines to natural killer-like cell-mediated cytotoxicity
1Department of Immunology, Mount Sinai Hospital Research Institute, Toronto, Ontario, Canada.
Abstract:
Multidrug resistance (MDR) refers to a complex phenotype that describes a number of features characterized primarily by resistance to a wide range of structurally unrelated drugs. In this paper we investigated the relationship between drug resistance and resistance to NK-mediated cytotoxicity. Studies with two independently selected multidrug-resistant cell lines indicated that increased drug resistance was associated with both an increased resistance to NK-mediated cytotoxicity and increased levels of membrane P-glycoprotein expression. This resistance to cytotoxicity appears to result partly from an alteration in the membrane structure of the target cells inasmuch as there was a reduction in effector:target cell recognition. Resistance to NK-mediated cytotoxicity should be included with the numerous pleiotropic changes associated with the multidrug resistance phenotype.
Insights
Multidrug resistance (MDR) is linked to reduced NK cell cytotoxicity. Increased drug resistance correlates with higher P-glycoprotein levels and impaired cell recognition, suggesting NK resistance is part of MDR.
Area of Science:
- Immunology
- Cell Biology
- Pharmacology
Background:
- Multidrug resistance (MDR) is a complex phenotype characterized by resistance to various drugs.
- Natural Killer (NK) cell-mediated cytotoxicity is a crucial component of the innate immune system.
Purpose of the Study:
- To investigate the relationship between multidrug resistance and resistance to NK-mediated cytotoxicity.
- To determine if drug resistance influences NK cell recognition and killing of target cells.
Main Methods:
- Utilized two independently selected multidrug-resistant cell lines.
- Assessed NK-mediated cytotoxicity and P-glycoprotein expression levels.
- Examined effector:target cell recognition.
Main Results:
- Increased drug resistance was associated with enhanced resistance to NK-mediated cytotoxicity.
- Higher levels of membrane P-glycoprotein expression were observed in multidrug-resistant cells.
- Reduced effector:target cell recognition contributed to NK resistance.
Conclusions:
- Resistance to NK-mediated cytotoxicity is a pleiotropic change associated with the multidrug resistance phenotype.
- Altered membrane structure in drug-resistant cells may impair NK cell recognition.
- NK cell resistance should be considered a characteristic feature of MDR.