Leukotriene B4 release from mast cells in IgE-mediated airway hyperresponsiveness and inflammation.

Published on Jun 1, 2009in American Journal of Respiratory Cell and Molecular Biology5.373
· DOI :10.1165/RCMB.2008-0095OC
Nobuaki Miyahara33
Estimated H-index: 33
,
Hiroshi Ohnishi20
Estimated H-index: 20
(University of Colorado Denver)
+ 9 AuthorsErwin W. Gelfand113
Estimated H-index: 113
(University of Colorado Denver)
Sources
Abstract
Previous studies have shown that leukotriene B4 (LTB4), a proinflammatory lipid mediator, is linked to the development of airway hyperresponsiveness through the accumulation of IL-13–producing CD8+ T cells, which express a high affinity receptor for LTB4, BLT1 (Miyahara et al., Am J Respir Crit Care Med 2005;172:161–167; J Immunol 2005;174:4979–4984). By using leukotriene A4 hydrolase–deficient (LTA4H−/−) mice, which fail to synthesize LTB4, we determined the role of this lipid mediator in allergen-induced airway responses. Two approaches were used. In the first, LTA4H−/− mice and wild-type (LTA4H+/+) mice were systemically sensitized and challenged via the airways to ovalbumin. In the second, mice were passively sensitized with anti-ovalbumin IgE and exposed to ovalbumin via the airways. Mast cells were generated from bone marrow of LTA4H+/+ mice or LTA4H−/− mice. After active sensitization and challenge, LTA4H−/− mice showed significantly lower airway hyperresponsiveness compared with LTA4H+/+ mice, and...
📖 Papers frequently viewed together
358 Citations
92 Citations
105 Citations
References53
Newest
#1Neil Ahluwalia (Harvard University)H-Index: 9
#2Alexander Y. Lin (Harvard University)H-Index: 9
Last. Robert E. GersztenH-Index: 84
view all 11 authors...
Leukotriene B 4 is a proinflammatory lipid mediator generated by the enzymes 5-lipoxygenase and leukotriene A 4 hydrolase. Leukotriene B 4 signals primarily through its high-affinity G protein-coupled receptor, BLT1, which is highly expressed on specific leukocyte subsets. Recent genetic studies in humans as well as knockout studies in mice have implicated the leukotriene synthesis pathway in several vascular pathologies. In this study, we tested the hypothesis that BLT1 is necessary for abdomin...
66 CitationsSource
Leukotrienes (LT) are a group of proinflammatory lipid mediators that are implicated in the pathogenesis and progression of atherosclerosis. Here we report that mRNA levels for the three key proteins in LTB4 biosynthesis, namely 5-lipoxygenase (5-LO), 5-LO-activating protein (FLAP), and LTA4 hydrolase (LTA4H), are significantly increased in human atherosclerotic plaque (n = 72) as compared with healthy controls (n = 6). Neither LTC4 synthase nor any of the LT receptors exhibits significantly inc...
216 CitationsSource
#1Wen-Hai Shao (University of Louisville)H-Index: 16
#2Annalisa Del Prete (University of Bari)H-Index: 24
Last. Bodduluri Haribabu (University of Louisville)H-Index: 55
view all 4 authors...
Leukotriene B4 mediates diverse inflammatory diseases through the G protein-coupled receptors BLT1 and BLT2. In this study, we developed mice deficient in BLT1 and BLT2 by simultaneous targeted disruption of these genes. The BLT1/BLT2 double-deficient mice developed normally and peritoneal exudate cells showed no detectable responses to leukotriene B4 confirming the deletion of the BLT1/BLT2 locus. In a model of collagen-induced arthritis on the C57BL/6 background, the BLT1/BLT2−/− as well as th...
92 CitationsSource
#1Nancy D. Kim (Harvard University)H-Index: 13
#2Richard C. Chou (Harvard University)H-Index: 8
Last. Andrew D. Luster (Harvard University)H-Index: 137
view all 5 authors...
Neutrophil recruitment into tissue plays an important role in host defense and disease pathogenesis, including the inflammatory arthritides. A multitude of diverse chemoattractants have been implicated in neutrophil recruitment, suggesting that they have overlapping functions in mediating this critical biological response. However, here we demonstrate a unique, non-redundant role for the leukotriene B4 receptor BLT1 in mediating neutrophil recruitment into the joint in the K/BxN mouse model of i...
221 CitationsSource
#1Christian TaubeH-Index: 51
#2Nobuaki MiyaharaH-Index: 33
Last. Erwin W. GelfandH-Index: 113
view all 11 authors...
Studies in both humans and rodents have suggested that CD8+ T cells contribute to the development of airway hyperresponsiveness (AHR) and that leukotriene B4 (LTB4) is involved in the chemotaxis of effector CD8+ T cells (TEFF) to the lung by virtue of their expression of BLT1, the receptor for LTB4. In the present study, we used a mast cell-CD8-dependent model of AHR to further define the role of BLT1 in CD8+ T cell-mediated AHR. C57BL/6+/+ and CD8-deficient (CD8−/−) mice were passively sensitiz...
92 CitationsSource
Antibody-antigen interactions in the airway initiate inflammation in acute asthma exacerbations. This inflammatory response is characterized by the recruitment of granulocytes into the airways. In murine models of asthma, granulocyte recruitment into the lung contributes to the development of airway hyperresponsiveness (AHR), mucus production, and airway remodeling. Leukotriene B4 is a mediator released following antigen challenge that has chemotactic activity for granulocytes, mediated through ...
33 CitationsSource
#1Nobuaki MiyaharaH-Index: 33
#2Satoko MiyaharaH-Index: 11
Last. Erwin W. GelfandH-Index: 113
view all 4 authors...
ABSTRACT LTB4, a proinflammatory lipid mediator generated from arachidonic acid through the action of 5-lipoxygenase, has been known for over two decades and is implicated in a wide variety of inflammatory disorders. BLT1, a G-protein-coupled receptor, has recently been identified as a high affinity receptor specific for LTB4. Recent studies in allergen-induced airway hyperresponsiveness and inflammation using mice lacking BLT1 have shown crucial new roles for leukotriene B4 and BLT1 in Th2 cyto...
58 CitationsSource
#1Kan Terawaki (UTokyo: University of Tokyo)H-Index: 11
#2Takehiko YokomizoH-Index: 53
Last. Takao ShimizuH-Index: 106
view all 8 authors...
Bronchial asthma is an increasingly common disorder that remains poorly understood and difficult to manage. The disease is characterized by airway hyperresponsiveness, chronic inflammation, and mucus overproduction. Based on the finding that leukotriene B 4 receptor 1 (BLT1) is expressed highly in Th2 lymphocytes, we analyzed the roles of BLT1 using an OVA-induced bronchial asthma model. BLT1-null mice did not develop airway hyperresponsiveness, eosinophilic inflammation, and hyperplasia of gobl...
147 CitationsSource
#1Eric A. Heller (Harvard University)H-Index: 3
#2Emerson LiuH-Index: 7
Last. Robert E. GersztenH-Index: 84
view all 14 authors...
Background— It is known that 5-lipoxygenase and its product, leukotriene B4 (LTB4), are highly expressed in several human pathologies, including atherosclerotic plaque. LTB4 signals primarily through its high-affinity G protein-coupled receptor BLT1, which is expressed on specific leukocyte subsets. BLT1 receptor expression and function on other atheroma-associated cell types is unknown. Methods and Results— To directly assess the role of the LTB4-BLT1 pathway in atherogenesis, we bred BLT1−/− m...
121 CitationsSource
#1Nobuaki MiyaharaH-Index: 33
#2Katsuyuki TakedaH-Index: 59
Last. Erwin W. Gelfand (National Jewish Health)H-Index: 113
view all 10 authors...
Rationale: Leukotriene B4 (LTB4) is a rapidly synthesized, early leukocyte chemoattractant that signals via its cell surface receptor, leukotriene B4 receptor 1 (BLT1), to attract and activate leukocytes during inflammation. A role for the LTB4–BLT1 pathway in allergen-induced airway hyperresponsiveness and inflammation is not well defined. Objectives: To define the role of the LTB4 receptor (BLT1) in the development of airway inflammation and altered airway function. Methods: BLT1-deficient (BL...
97 CitationsSource
Cited By39
Newest
Grifola frondosa (G. frondosa) is an edible mushroom consumed as a health food in Asia that has recently been reported to have anti-allergic effects. In this study, we investigated the effects of G...
Source
#1Shin Ae Kang (PNU: Pusan National University)H-Index: 12
#2Hak Sun Yu (PNU: Pusan National University)H-Index: 27
AIMS Helminth infection typically induces a Th2 inflammatory response that is characterized by eosinophilia, high levels of IgE, and mast cells. LTB4 is generated from innate immune cells, such as neutrophils, macrophages, and mast cells, in response to a range of stimuli. It mainly acts on myeloid leukocytes, inducing the activation of integrins, adhesion to endothelium walls, and chemotaxis. METHODS AND RESULTS The objective of the present study was to determine the role of the LTB4 receptor i...
Source
#1Wei-Jie Li (ZJU: Zhejiang University)H-Index: 1
#2Yun Zhao (ZJU: Zhejiang University)H-Index: 9
Last. Huahao Shen (ZJU: Zhejiang University)H-Index: 33
view all 7 authors...
Abstract Asthma is a chronic inflammatory disease of the lungs that poses a considerable health and socioeconomic burden. Several risk factors work synergistically to affect the progression of asthma. Lipid metabolism, especially in distinct cells such as T cells, macrophages, granulocytes, and non-immune cells, plays an essential role in the pathogenesis of asthma, as lipids are potent signaling molecules that regulate a multitude of cellular response. In this review, we focused on the metaboli...
Source
#1Rui He (Fudan University)H-Index: 24
#2Yu Chen (Fudan University)H-Index: 1
Last. Qian Cai (Fudan University)H-Index: 2
view all 3 authors...
Abstract Leukotriene B4 (LTB4) is a major type of lipid mediator that is rapidly generated from arachidonic acid through sequential action of 5-lipoxygenase (5-LO), 5-lipoxygenase-activating protein (FLAP) and LTA4 hydrolase (LTA4H) in response to various stimuli. LTB4 is well known to be a chemoattractant for leukocytes, particularly neutrophils, via interaction with its high-affinity receptor BLT1. Extensive attention has been paid to the role of the LTB4-BLT1 axis in acute and chronic inflamm...
4 CitationsSource
#1Hong Ki Min (Konkuk University)H-Index: 7
#2Kyoung-Woon Kim (Catholic University of Korea)H-Index: 15
Last. Hae-Rim Kim (Konkuk University)H-Index: 20
view all 4 authors...
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory arthritis, and the complex interaction and activation of innate and adaptive immune cells are involved in RA pathogenesis. Mast cells (MCs) are one of the tissue-resident innate immune cells, and they contribute to RA pathogenesis. In the present review, the evidence of the pathologic role of MC in RA is discussed based on human and animal data. In addition, the potential role of MC in RA pathogenesis and the research area that shoul...
6 CitationsSource
#1Timothy S.C. Hinks (NIHR: National Institute for Health Research)H-Index: 23
#2Ryan D. Hoyle (NIHR: National Institute for Health Research)H-Index: 1
Last. Erwin W. GelfandH-Index: 113
view all 3 authors...
The complexity of asthma is underscored by the number of cell types and mediators implicated in the pathogenesis of this heterogeneous syndrome. Type 2 CD4+ T-cells (Th2) and more recently, type 2 innate lymphoid cells dominate current descriptions of asthma pathogenesis. However, another important source of these type 2 cytokines, especially interleukin (IL)-5 and IL-13, are CD8+ T-cells, which are increasingly proposed to play an important role in asthma pathogenesis, because they are abundant...
12 CitationsSource
#1Vincenzo SimonettiH-Index: 5
Last. Luigi Valdenassi (UNIPV: University of Pavia)H-Index: 5
view all 6 authors...
Introduction. Skin reactions and cardiotoxicity are one of the most common side effects of doxorubicin in cancer patients. The main mechanisms based on the etiopathogenesis of these reactions are mediated by the overproduction of proinflammatory cytokines, metalloproteases, and the disruption of mitochondrial homeostasis. Ozone therapy demonstrated anti-inflammatory effects in several preclinical and clinical studies. The aim of this research is based on the evaluation of cardioprotective and de...
11 CitationsSource
#1Erika Mendez‐Enriquez (Uppsala University)H-Index: 6
#2Jenny Hallgren (Uppsala University)H-Index: 24
Mast cells and their mediators have been implicated in the pathogenesis of asthma and allergy for decades. Allergic asthma is a complex chronic lung disease in which several different immune cells, genetic factors and environmental exposures influence the pathology. Mast cells are key players in the asthmatic response through secretion of a multitude of mediators with pro-inflammatory and airway-constrictive effects. Well-known mast cell mediators, such as histamine and bioactive lipids are resp...
40 CitationsSource
#1Yingluo Xiong (Fudan University)H-Index: 6
#2Xinyi Cui (Fudan University)H-Index: 3
Last. Rui He (Fudan University)H-Index: 24
view all 11 authors...
BACKGROUND: Epithelial cells (ECs) play a crucial role in allergic sensitization to inhaled protease allergens by instructing type 2 innate lymphoid cells (ILC2) and dendritic cells (DCs) via release of pro-type 2 cytokines, particularly interleukin-33 (IL-33). Leukotriene B4 (LTB4) is a well-known leukocyte chemoattractant via engagement of its receptor 1 (BLT1). However, the role of LTB4-BLT1 axis in allergic sensitization via activation of ECs is still unknown. METHODS: We evaluated the effec...
16 CitationsSource
#1Sobha R. Bodduluri (University of Louisville)H-Index: 7
#2Steven P. Mathis (University of Louisville)H-Index: 10
Last. Bodduluri Haribabu (University of Louisville)H-Index: 55
view all 12 authors...
The presence of mast cells in some human colorectal cancers is a positive prognostic factor, but the basis for this association is incompletely understood. Here, we found that mice with a heterozygous mutation in the adenomatous polyposis coli gene (Apc Min/+ ) displayed reduced intestinal tumor burdens and increased survival in a chemokine decoy receptor, ACKR2-null background, which led to discovery of a critical role for mast cells in tumor defense. ACKR2 −/− Apc Min/+ tumors showed increased...
17 CitationsSource