Lipid-cytokine-chemokine cascade drives neutrophil recruitment in a murine model of inflammatory arthritis.

Lipid-cytokine-chemokine cascade drives neutrophil recruitment in a murine model of inflammatory arthritis.
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DOI:
10.1016/j.immuni.2010.07.018
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发表时间:
2010-08-27
期刊:
影响因子:
32.4
通讯作者:
Luster AD
Luster AD
中科院分区:
医学1区
文献类型:
--
作者:
Chou RC;Kim ND;Sadik CD;Seung E;Lan Y;Byrne MH;Haribabu B;Iwakura Y;Luster AD

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A large and diverse array of chemoattractants control leukocyte trafficking, but how these apparently redundant signals collaborate in vivo is still largely unknown. We previously demonstrated an absolute requirement for the lipid chemoattractant leukotriene B4 (LTB4) and its receptor BLT1 for neutrophil recruitment into the joint in autoantibody-induced arthritis. We now demonstrate that BLT1 is required for neutrophils to deliver IL-1 into the joint to initiate arthritis. IL-1-expressing neutrophils amplify arthritis through the production of neutrophil-active chemokines from synovial tissue cells. CCR1 and CXCR2, two neutrophil chemokine receptors, operate non-redundantly to sequentially control the later phase of neutrophil recruitment into the joint and mediate all neutrophil chemokine activity in the model. Thus, we have uncovered a complex sequential relationship involving unique contributions from the lipid mediator LTB4, the cytokine IL-1, and CCR1 and CXCR2 chemokine ligands that are all absolutely required for effective neutrophil recruitment into the joint.
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