Volume 7 Supplement 1
Differential expression of multidrug resistance-related proteins on monocyte-derived macrophages from rheumatoid arthritis patients
© BioMed Central Ltd 2005
Received: 11 January 2005
Published: 17 February 2005
Primary or acquired drug resistance is well recognized as a common cause of treatment failure of patients with cancer. From a rheumatoid arthritis (RA) perspective, the issue of resistance to anti-rheumatic drugs (e.g. disease-modifying anti-rheumatic drugs [DMARDs]) has not received much attention. A possible mechanism of drug resistance is overexpression of multidrug resistance (MDR)-related proteins. The objective of this study was to identify whether various MDR proteins are expressed on macrophages as potential target cells for DMARDs.
Monocyte-derived macrophages (MDM) were obtained from 15 RA patients (median age: 56 years, 13 females/two males) and eight healthy controls (median age: 51 years, four females/four males). Monocytes were isolated from peripheral blood mononuclear cells and differentiated into macrophages in the presence of monocyte-colony stimulating factor. Cytospins of MDMs were prepared for immunohistological analysis of the MDR-related proteins: P-glycoprotein, multidrug resistance associated protein (MRP) 1, MRP4, MRP5, breast cancer resistance protein (BCRP) and lung resistance protein (LRP). Staining intensities were scored as follows: (0), negative; (1), weakly positive; (2), positive; (3), strongly positive. The total score is depicted as the summation of percentiles of cells with intensities 0–3.
Multidrug resistance (MDR) protein expression in monocyte-derived macrophages from rheumatoid arthritis patients and healthy controls as median scores (ranges)
Rheumatoid arthritis patients (n = 15)
Controls (n = 8)
MDR proteins, known to be involved in conferring drug resistance, are expressed on macrophages of RA patients. Beyond this, there seems to be a trend for a higher expression of MDR proteins on MDM from RA patients compared with healthy controls. Further studies are warranted to assess whether MDR is a clinically relevant issue in daily treatment of RA patients.
This study is supported by the Dutch Arthritis Association (Grant NRF-03-I-40).