The Multidrug Resistance Protein 1: A Functionally Important Activation Marker for Murine Th1 Cells

Prechtl, Stefan; Roellinghoff, M; Scheper, Rik J.; Cole, Susan P. C.; Deeley, Roger G.; Lohoff, Michael

doi:10.4049/jimmunol.164.2.754

Cited by 35 publications

(28 citation statements)

References 38 publications

(38 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To confirm that MK571 inhibited ABCC1-mediated transport, cells were loaded with Fluo-3AM, a fluorescent dye that is transported out of the cell by ABCC1 (22,25). In agreement with other reports (22,25), only MK571, and not PSC833 or verapamil, inhibited Fluo-3 efflux (Fig. 2D).…”

supporting

confidence: 64%

“…Another ABC family member, ABCC1, selectively transports C 6 (N-6[7-nitro-2,1,3-benzoxadiazol-4yl] aminohexanoyl) (NBD)-glucosylceramide and C 6 -NBD-sphingomyelin (24). To explore ABCC1's potential role in the export of S1P, RBL-2H3 cells were treated with MK571, an ABCC1-specific inhibitor (25,26). MK571 inhibited S1P secretion by vector and SphK1 transfected RBL-2H3 cells (Fig.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Role of ABCC1 in export of sphingosine-1-phosphate from mast cells

Mitra

Oskeritzian

Payne

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

379

329

View full text Add to dashboard Cite

Mast cells play a pivotal role in inflammatory and immediate-type allergic reactions by secreting a variety of potent inflammatory mediators, including sphingosine-1-phosphate (S1P). However, it is not known how S1P is released from cells. Here, we report that S1P is exported from mast cells independently of their degranulation and demonstrate that it is mediated by ATP binding cassette (ABC) transporters. Constitutive and antigen-stimulated S1P release was inhibited by MK571, an inhibitor of ABCC1 (MRP1), but not by inhibitors of ABCB1 (MDR-1, P-glycoprotein). Moreover, downregulation of ABCC1 with small interfering RNA, which decreased its cell surface expression, markedly reduced S1P export from both rat RBL-2H3 and human LAD2 mast cells. Transport of S1P by ABCC1 influenced migration of mast cells toward antigen but not degranulation. These findings have important implications for S1P functions in mast cell-mediated immune responses.secretion ͉ sphingolipids ͉ multidrug resistance ͉ allergic responses ͉ sphingosine kinase S phingosine-1-phosphate (S1P) is a pleiotropic lipid mediator that has been implicated in cancer, immunity, and allergy (1-4). S1P is a ligand for a family of five specific G protein-coupled receptors, designated S1P 1-5 (collectively referred to as S1PRs) (5), through which it regulates many different biological responses, including growth, survival, differentiation, cytoskeleton rearrangements, motility, angiogenesis, vascular maturation, lymphocyte trafficking, and mast cell functions (reviewed in refs. 1-3, 5, and 6). Moreover, like its precursors, sphingosine (Sph) and ceramide, S1P may also have intracellular functions (1, 2, 7). S1P is produced in cells by phosphorylation of Sph, the backbone of all sphingolipids, catalyzed by two closely related Sph kinase (SphK) isoenzymes. SphK1 activity is enhanced by numerous external stimuli, including growth factors, ligands for G protein-coupled receptors, and proinflammatory cytokines, and by cross-linking of Ig receptors (reviewed in refs. 1 and 6). To date, only EGF (8) and cross-linking of Ig receptors (4) have been shown to stimulate SphK2.Although S1P secretion has been demonstrated in only a few types of cells (platelets, astroglial cells, and mast cells) activation of SphK1 involves its translocation to the plasma membrane where its substrate Sph resides (9 -11). Increased S1P formation, in turn, activates S1P receptors on the same and͞or neighboring cells in an autocrine or paracrine manner. It has been demonstrated that this type of ''inside-out'' signaling by S1P is critical for migratory responses of fibroblasts and smooth muscle cells toward PDGF (9, 12) and human breast cancer cells toward EGF (8). Similarly, S1P secreted by mast cells is important for migration of mast cells toward antigen (Ag) and might be involved in the movement of mast cells to sites of inf lammation (13). In addition, S1P provokes human airway smooth muscle contraction and may promote inf lammation and airway remodeling in asthma (14). Because S1P's level...

show abstract

supporting

confidence: 64%

mentioning

confidence: 99%

Role of ABCC1 in export of sphingosine-1-phosphate from mast cells

Mitra

Oskeritzian

Payne

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

379

329

View full text Add to dashboard Cite

show abstract

“…Mrp1 has been implicated in inflammatory and infectious diseases because of its expression on activated Th1 lymphocytes (Prechtl et al, 2000) and its ability to transport signaling mediators (such as leukotrienes and glutathione) Wijnholds et al, 1997). Although Mrp1 is expressed on activated Th1 lymphocytes, it is not necessary for activation of this immune cell population (Kleemann et al, 2006).…”

Section: Inflammationmentioning

confidence: 99%

Xenobiotic, Bile Acid, and Cholesterol Transporters: Function and Regulation

2010

View full text Add to dashboard Cite

“…It has been reported that the fluorescent anion Fluo-3 can be used to monitor MRP1 activity. 17 In the present experiments, nearly half of the BMMC population was able to transport Fluo-3 (Fig. 1b,c).…”

Section: Mrp-related Transport Activitymentioning

confidence: 75%

“…4 Moreover, these proteins were described in thymocytes, [5][6][7] mature lymphocytes, 8,9 dendritic cells, 10,11 monocytes 12 and macrophages. 13 It has been suggested that multidrug transporters may play a role in the cells of the immune system, mediating the efflux of xenobiotics 14,15 and regulating cell activation [16][17][18] and migration. 10,11 Haematopoietic stem cells (HSC) comprise approximately 0Á05% of bone marrow (BM).…”

mentioning

confidence: 99%