Microparticles mediate enzyme transfer from platelets to mast cells: a new pathway for lipoxin A4 biosynthesis.
The inflammation-resolving lipid mediator lipoxin A4 (LXA4), which is derived from arachidonic acid in the context of inflammation, can be generated physiologically in vivo. However, the mechanism of physiologic formation of LXA4 remains elusive. In this report, we provide evidence that platelet-derived microparticles contain lipoxygenase 12 (12-LO) protein and act as a mediator in transferring 12-LO to mast cells, leading to the production of LXA4 by mast cells. Absence of either leukotriene, the precursor for LXA4, in mast cells or 12-LO in microparticles abolished LXA4 production. Using a mouse model, we demonstrated that platelet-derived microparticles were taken up by peritoneal mast cells in vivo and triggered LXA4 production. We also found that similar to LXA4, platelet-derived microparticles attenuated LPS- or dextran sulfate sodium-induced inflammation by regulating inflammatory cytokines. Together, these data suggest a critical role of platetlet-derived microparticles as a signal mediator, at least in LXA4 production, resulting in significant immunoregulatory consequences.
Tang
Ke
K
Department of Pathophysiology, Tonji Medical College, Huazhong University of Science & Technology, Wuhan 430030, PR China.
Liu
Jing
J
Yang
Zhuoshun
Z
Zhang
Biao
B
Zhang
Huafeng
H
Huang
Chunmei
C
Ma
Jingwei
J
Shen
Guan-Xin
GX
Ye
Duyun
D
Huang
Bo
B
D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism*; D001792:Blood Platelets / Q000201:enzymology*; D055252:Cell-Derived Microparticles / Q000201:enzymology*; D016264:Dextran Sulfate / Q000633:toxicity; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000517:prevention & control; D044045:Lipoxins / Q000008:administration & dosage / Q000096:biosynthesis*; D008407:Mast Cells / Q000201:enzymology*; D051379:Mice; D008817:Mice, Mutant Strains; D021381:Protein Transport
D044045:Lipoxins; C040527:lipoxin A4; D016264:Dextran Sulfate; D001092:Arachidonate 12-Lipoxygenase