TY - JOUR
T1 - The leukotriene C4 transporter MRP1 regulates CCL19 (MIP-3β, ELC)-dependent mobilization of dendritic cells to lymph nodes
AU - Robbiani, Davide F.
AU - Finch, Rick A.
AU - Jäger, Dirk
AU - Muller, William A.
AU - Sartorelli, Alan C.
AU - Randolph, Gwendalyn J.
N1 - Funding Information:
We are indebted to Dr. Marco Baggiolini (Theodor Kocher Institut, Bern, Switzerland) for graciously providing human recombinant CCL19 and CXCL12 and to Dr. M. D. Gunn (Duke University Medical Center, Durham, NC) for the generous gift of human recombinant CCL21, and thank Dr. Elisabetta Dejana (Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy) for mAb to cadherin 5 and Dr. Siamon Gordon (University of Oxford) for anti-macrophage mAb SER-4. We are also grateful to Drs. Sylvie Beaulieu, Kayo Inaba, and Alan Schenkel for helpful contributions, and thank Drs. Lloyd Hoffman (New York Presbyterian Hospital) and Nancy Gallo (New York Firefighter's Skin Bank) for preparing and providing human split-thickness skin. This research was supported by a Scientist Development Grant (930118N) to G. J. R. from the American Heart Association (National Affiliate). D. F. R. was the recipient of a travel award from the Dr. Ettore Balli Foundation, Bellinzona, Switzerland.
PY - 2000/11/22
Y1 - 2000/11/22
N2 - Adaptive immune responses begin after antigen-bearing dendritic cells (DCs) traffic from peripheral tissues to lymph nodes. Here, we show that DC migration from skin to lymph nodes utilizes the leukotriene C4 (LTC4) transporter multidrug resistance-associated protein 1 (MRP1). DC mobilization from the epidermis and trafficking into lymphatic vessels was greatly reduced in MRP1(-/-) mice, but migration was restored by exogenous cysteinyl leukotrienes LTC4 or LTD4. In vitro, these cysteinyl leukotrienes promoted optimal chemotaxis to the chemokine CCL19, but not to other related chemokines. Antagonism of CCL19 in vivo prevented DC migration out of the epidermis. Thus, MRP-1 regulates DC migration to lymph nodes, apparently by transporting LTC4, which in turn promotes chemotaxis to CCL19 and mobilization of DCs from the epidermis.
AB - Adaptive immune responses begin after antigen-bearing dendritic cells (DCs) traffic from peripheral tissues to lymph nodes. Here, we show that DC migration from skin to lymph nodes utilizes the leukotriene C4 (LTC4) transporter multidrug resistance-associated protein 1 (MRP1). DC mobilization from the epidermis and trafficking into lymphatic vessels was greatly reduced in MRP1(-/-) mice, but migration was restored by exogenous cysteinyl leukotrienes LTC4 or LTD4. In vitro, these cysteinyl leukotrienes promoted optimal chemotaxis to the chemokine CCL19, but not to other related chemokines. Antagonism of CCL19 in vivo prevented DC migration out of the epidermis. Thus, MRP-1 regulates DC migration to lymph nodes, apparently by transporting LTC4, which in turn promotes chemotaxis to CCL19 and mobilization of DCs from the epidermis.
UR - http://www.scopus.com/inward/record.url?scp=0034703712&partnerID=8YFLogxK
U2 - 10.1016/S0092-8674(00)00179-3
DO - 10.1016/S0092-8674(00)00179-3
M3 - Article
C2 - 11114332
AN - SCOPUS:0034703712
SN - 0092-8674
VL - 103
SP - 757
EP - 768
JO - Cell
JF - Cell
IS - 5
ER -