Abstract
Mast cells are effector cells in the immune system that play an important role in the allergic airway inflammation. Recently, it was reported that BLT2, a low-affinity leukotriene (LT) B4 receptor, plays a pivotal role in the pathogenesis of allergic airway inflammation through its action in mast cells. We observed that highly elevated expression levels of BLT2 are critical for the pathogenesis leading to allergic airway inflammation, and that if BLT2 expression is downregulated by siBLT2-mediated knockdown, allergic inflammation is dramatically alleviated. Furthermore, we demonstrated that BLT2 mediates the synthesis of vascular endothelial growth factor (VEGF) and Th2 cytokines, such as interleukin (IL)-13, in mast cells during allergic inflammation. Based on the critical roles of BLT2 in mast cells in allergic inflammation, anti-BLT2 strategies could contribute to the development of new therapies for allergic airway inflammation.
Highlights
Mast cells are multifunctional cells in the immune system that were first identified in 1878 by Paul Ehrlich, who was awarded the Nobel Prize in Physiology or Medicine in 1908 [1,2]
We demonstrated that the Nox1-reactive oxygen species (ROS)-NF-κB cascade is downstream of BLT2 during Ag signaling to vascular endothelial growth factor (VEGF) synthesis in mast cells, implying that BLT2 mediates the synthesis of VEGF through the Nox1-ROS-NF-κB cascade in Ag-stimulated mast cells [21]
VEGF levels were much enhanced by treatment with BLT2 ligands in bone marrow-derived mast cells (BMMC) derived from BLT2 TG mice [21]
Summary
Mast cells are multifunctional cells in the immune system that were first identified in 1878 by Paul Ehrlich, who was awarded the Nobel Prize in Physiology or Medicine in 1908 [1,2]. Mast cells play roles in the pathophysiology of the allergic airway inflammation in asthma [7,8]. Previous studies suggested that mast cells play a role in neoplastic angiogenesis through the expression of vascular endothelial growth factors (VEGFs) and their receptors [9,10]. Previous studies have reported that both BLT1 and BLT2 are expressed in human and murine mast cells, and that both receptors contribute to the chemotactic migration of mast cells toward LTB4 [18,19]. Previous studies have suggested that BLT2 plays a mediatory role in the pathogenesis of the allergic airway inflammation in asthma through its action in mast cells [20,21,22,23]. This review focuses on the recently discovered novel roles of BLT2 in mast cells during allergic airway inflammation
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