BLT1 and BLT2: the leukotriene B4 receptors

doi:10.1016/S0952-3278(03)00073-5

Prostaglandins, Leukotrienes and Essential Fatty Acids

Volume 69, Issues 2–3, August–September 2003, Pages 123-134

https://doi.org/10.1016/S0952-3278(03)00073-5 Get rights and content

Abstract

Two receptors for leukotriene B₄ (LTB₄) have been molecularly identified: BLT1 and BLT2. Both receptors are G protein-coupled seven transmembrane domain receptors, whose genes are located in very close proximity to each other in the human and mouse genomes. The two receptors differ in their affinity and specificity for LTB₄: BLT1 is a high-affinity receptor specific for LTB₄, whereas BLT2 is a low-affinity receptor that also binds other eicosanoids. The two receptors also differ in their pattern of expression with BLT1 being expressed primarily in leukocytes, whereas BLT2 is expressed more ubiquitously. By mediating the activities of LTB₄, these receptors participate both in host immune responses and in the pathogenesis of inflammatory diseases. Reduced disease severity in animal inflammatory models seen with LTB₄ receptor antagonists and in mice with targeted deletion of BLT1 have revealed important roles for LTB₄ and its receptors in regulating pathologic inflammation.

Introduction

Leukotriene B₄ (LTB₄) is an extremely potent lipid inflammatory mediator derived from membrane phospholipids by the sequential actions of cytosolic phospholipase A₂, 5-lipoxygenase (5-LO) and LTA₄ hydrolase. The major activities of LTB₄ include the recruitment and activation of leukocytes, suggesting that it has considerable functional overlap with the chemokine family of chemoattractant peptides, which also direct the recruitment of leukocytes. Though structurally completely different, the lipid LTB₄ and the peptide chemokines mediate their function through the same class of receptors, the G protein-coupled seven transmembrane domain receptor (GPCR) superfamily. Two GPCRs for LTB₄ have been identified, BLT1 and BLT2. By mediating the activities of LTB₄, these receptors participate both in the recruitment and activation of leukocytes as part of host immune responses to invading pathogens, as well as in the pathogenesis of inflammatory diseases in which LTB₄ has been implicated.

Section snippets

BLT1

LTB₄ was initially discovered by Borgeat and Samuelsson [1], and found to be a potent neutrophil chemoattractant by Ford-Hutchinson et al. [2]. A high-affinity binding site for [³H]LTB₄ on human neutrophils was initially detected [3], with a K_d found by different investigators to be 0.39 nM [4], 0.46 nM [5], and 1.5 nM [6]. Molecular identification of a receptor for LTB₄ eluded investigators for many years, however, until the human high-affinity LTB₄ receptor was finally cloned by Yokomizo et al.

Affinity for ligand(s) and cytoplasmic signaling cascades

As noted above, the K_d value for LTB₄ binding of membrane fractions of HEK 293 cells transfected with human BLT2 is 20-fold higher than the K_d for membrane fractions of human BLT1 transfectants [16]. Consistent with BLT2 being a low-affinity receptor, the dose–response curve of LTB₄-induced increases in intracellular calcium in human BLT2-transfected CHO cells was shifted right by two orders of magnitude compared with human BLT1 transfectants [16]. Similarly, the LTB₄ concentration inducing

Expression and regulation

Northern blotting of various human tissues with human BLT1 cDNA demonstrated that BLT1 expression is highest in peripheral blood leukocytes and is present in much lower amounts in spleen, thymus, bone marrow, lymph nodes, heart, skeletal muscle, brain, and liver [7], [10], [12]. Human BLT1 protein expression has been confirmed by flow cytometry using anti-BLT1 monoclonal antibodies on CD15+ peripheral blood granulocytes, and on HL-60 cells when differentiated into neutrophil-like cells by

Main activities and pathophysiological roles of LTB₄

BLT1 and BLT2 may play critical roles in both host defense and in many inflammatory diseases by mediating the multiple activities of LTB₄. Activities of LTB₄ include inflammatory cell recruitment, activation of inflammatory cell effector functions, and prolongation of inflammatory cell survival.

Assignment of LTB₄ activities to BLT1 and BLT2

Both BLT1 and BLT2 mediate LTB₄-induced activities in stable CHO cell transfectants, including chemotaxis, rapid increases in intracellular calcium concentration, and inhibition of forskolin-stimulated adenylyl cyclase activity [7], [8], [16]. Generation of two lines of BLT1-deficient mice by targeted gene disruption [92], [93] has allowed investigators to determine that several of the major activities of LTB₄ on leukocytes are mediated by BLT1 in the mouse (Table 1). LTB₄-induced chemotaxis is

Conclusions

Two different GPCRs, BLT1 and BLT2, that exist in a gene cluster in humans and mice have been identified as receptors for the potent lipid inflammatory mediator LTB₄. As noted, these receptors differ significantly in their affinity and specificity for LTB₄, as well as in the distribution of their expression. Experiments with BLT1^−/− mice indicate that BLT1 mediates the major activities of LTB₄ on leukocytes, including directed migration and conversion of rolling to firm adhesion. The biological

Acknowledgments

Dr. Tager and Dr. Luster gratefully acknowledge grant support from the National Institutes of Health and the Dana Foundation.

References (95)

P. Borgeat et al.
Transformation of arachidonic acid by rabbit polymorphonuclear leukocytes. Formation of a novel dihydroxyeicosatetraenoic acid
J. Biol. Chem.
(1979)
A.H. Lin et al.
Leukotriene B₄ binding to human neutrophils
Prostaglandins
(1984)
J.S. Bomalaski et al.
Binding of leukotriene B₄ and its analogs to human polymorphonuclear leukocyte membrane receptors
Prostaglandins
(1987)
C. Owman et al.
Cloning of cDNA encoding a putative chemoattractant receptor
Genomics
(1996)
C. Owman et al.
Leukotriene B₄ is the functional ligand binding to and activating the cloned chemoattractant receptor, CMKRL1
Biochem. Biophys. Res. Commun.
(1997)
G.K. Akbar et al.
Molecular cloning of a novel P2 purinoceptor from human erythroleukemia cells
J. Biol. Chem.
(1996)
V. Martin et al.
Leukotriene binding, signaling, and analysis of HIV coreceptor function in mouse and human leukotriene B₄ receptor-transfected cells
J. Biol. Chem.
(1999)
Y. Yamada et al.
Human somatostatin receptor geneslocalization to human chromosomes 14 17 and 22 and identification of simple tandem repeat polymorphisms
Genomics
(1993)
Y. Tryselius et al.
Characterization of cDNA encoding a novel human leukotriene B(4) receptor
Biochem. Biophys. Res. Commun.
(2000)
M. Kamohara et al.
Molecular cloning and characterization of another leukotriene B₄ receptor
J. Biol. Chem.
(2000)

N.E. Nilsson et al.

Genomic organization of the leukotriene B(4) receptor locus of human chromosome 14

Biochem. Biophys. Res. Commun.

(2000)

Y. Le et al.

Formyl-peptide receptors revisited

Trends Immunol.

(2002)

J.L. Gao et al.

Differential expansion of the N-formylpeptide receptor gene cluster in human and mouse

Genomics

(1998)

T. Yokomizo et al.

Hydroxyeicosanoids bind to and activate the low-affinity leukotriene B₄ receptor BLT2

J. Biol. Chem.

(2001)

K. Kishikawa et al.

ONO-4057 a novel orally active leukotriene B₄ antagonisteffects on ltb4-induced neutrophil functions

Prostaglandins

(1992)

A. Pettersson et al.

First-generation monoclonal antibodies identifying the human leukotriene B(4) receptor-1

Biochem. Biophys. Res. Commun.

(2000)

S.T. Smale et al.

The initiator as a transcription control element

Cell

(1989)

N.A. Soter et al.

Local effects of synthetic leukotrienes (LTC₄, LTD₄, LTE₄, and LTB₄) in human skin

J. Invest. Dermatol.

(1983)

R. Sehmi et al.

Interleukin-5 selectively enhances the chemotactic response of eosinophils obtained from normal but not eosinophilic subjects

Blood

(1992)

A. Coxon et al.

A novel role for the beta 2 integrin CD11b/CD18 in neutrophil apoptosisa homeostatic mechanism in inflammation

Immunity

(1996)

J.P. van Pelt et al.

The regulation of CD11b integrin levels on human blood leukocytes and leukotriene B₄stimulated skin by a specific leukotriene B4 receptor antagonist (LY293111)

Biochem. Pharmacol.

(1997)

H. Sumimoto et al.

Superoxide production of human polymorphonuclear leukocytes stimulated by leukotriene B₄

Biochim. Biophys. Acta

(1984)

T. Demitsu et al.

Phagocytosis and bactericidal action of mouse peritoneal macrophages treated with leukotriene B₄

Int. J. Immunopharmacol.

(1989)

F. Arcoleo et al.

Effect of exogenous leukotriene B₄ (LTB₄) on BALB/c mice splenocyte production of Th1 and Th2 lymphokines

Int. J. Immunopharmacol.

(1995)

H. Morita et al.

Immunosuppressive effect of leukotriene B(4) receptor antagonist in vitro

Biochem. Biophys. Res. Commun.

(1999)

M. Rola-Pleszczynski et al.

Leukotriene B₄ augments human natural cytotoxic cell activity

Biochem. Biophys. Res. Commun.

(1983)

R. Renkonen et al.

Leukotriene B₄ increases the lymphocyte binding to endothelial cells

FEBS Lett.

(1988)

C. Bortuzzo et al.

The effect of leukotrienes B and selected HETEs on the proliferation of colon cancer cells

Biochim. Biophys. Acta

(1996)

R. Hennig et al.

5-Lipoxygenase and leukotriene B(4) receptor are expressed in human pancreatic cancers but not in pancreatic ducts in normal tissue

Am. J. Pathol.

(2002)

H. Hopkins et al.

Neutrophil chemotactic factors in bacterial pneumonia

Chest

(1989)

P. Montuschi et al.

Exhaled leukotrienes and prostaglandins in asthma

J. Allergy Clin. Immunol.

(2002)

P. Sharon et al.

Enhanced synthesis of leukotriene B₄ by colonic mucosa in inflammatory bowel disease

Gastroenterology

(1984)

E.A. Duell et al.

Determination of 5, 12, and 15-lipoxygenase products in keratomed biopsies of normal and psoriatic skin

J. Invest. Dermatol.

(1988)

A.W. Ford-Hutchinson et al.

Apotent chemokinetic aggregating substance released from polymorphonuclear leukocytes

Nature

(1980)

D.W. Goldman et al.

Specific binding of leukotriene B₄ to receptors on human polymorphonuclear leukocytes

J. Immunol.

(1982)

D.W. Goldman et al.

Heterogeneity of human polymorphonuclear leukocyte receptors for leukotriene B₄. Identification of a subset of high affinity receptors that transduce the chemotactic response

J. Exp. Med.

(1984)

T. Yokomizo et al.

AG-protein-coupled receptor for leukotriene B₄ that mediates chemotaxis

Nature

(1997)

W.W. Huang et al.

Molecular and biological characterization of the murine leukotriene B₄ receptor expressed on eosinophils

J. Exp. Med.

(1998)

C.J. Raport et al.

New members of the chemokine receptor gene family

J. Leukocyte Biol.

(1996)

P.M. Murphy

The molecular biology of leukocyte chemoattractant receptors

Annu. Rev. Immunol.

(1994)

T. Yokomizo et al.

Second leukotriene B(4) receptor BLT2a new therapeutic target in inflammation and immunological disorders [see comments]

J. Exp. Med.

(2000)

S. Wang et al.

A novel hepatointestinal leukotriene B₄ receptorcloning and functional characterization

J. Biol. Chem.

(2000)

S.K. Ahuja et al.

Molecular evolution of the human interleukin-8 receptor gene cluster

Nature Genet.

(1992)

H.J. Showell et al.

The in vitro and in vivo pharmacologic activity of the potent and selective leukotriene B₄ receptor antagonist CP-105696

J. Pharmacol. Exp. Ther.

(1995)

H.J. Showell et al.

The preclinical pharmacological profile of the potent and selective leukotriene B₄ antagonist CP-195543

J. Pharmacol. Exp. Ther.

(1998)

C.F. Lawson et al.

Receptor antagonism of leukotriene B₄ myotropic activity by the 26 disubstituted pyridine analog U-75302characterization on lung parenchyma strips

J. Lipid Mediat.

(1989)

D.K. Herron et al.

Leukotriene B₄ receptor antagoniststhe ly255283 series of hydroxyacetophenones

J. Med. Chem.

(1992)

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BLT1 and BLT2: the leukotriene B4 receptors

Abstract

Introduction

Section snippets

BLT1

Affinity for ligand(s) and cytoplasmic signaling cascades

Expression and regulation

Main activities and pathophysiological roles of LTB4

Assignment of LTB4 activities to BLT1 and BLT2

Conclusions

Acknowledgments

J. Biol. Chem.

Prostaglandins

Prostaglandins

Genomics

Biochem. Biophys. Res. Commun.

J. Biol. Chem.

J. Biol. Chem.

Genomics

Biochem. Biophys. Res. Commun.

J. Biol. Chem.

Biochem. Biophys. Res. Commun.

Trends Immunol.

Genomics

J. Biol. Chem.

Prostaglandins

Biochem. Biophys. Res. Commun.

Cell

J. Invest. Dermatol.

Blood

Immunity

Biochem. Pharmacol.

Biochim. Biophys. Acta

Int. J. Immunopharmacol.

Int. J. Immunopharmacol.

Biochem. Biophys. Res. Commun.

Biochem. Biophys. Res. Commun.

FEBS Lett.

Biochim. Biophys. Acta

Am. J. Pathol.

Chest

J. Allergy Clin. Immunol.

Gastroenterology

J. Invest. Dermatol.

Apotent chemokinetic aggregating substance released from polymorphonuclear leukocytes

Nature

Specific binding of leukotriene B4 to receptors on human polymorphonuclear leukocytes

J. Immunol.

Heterogeneity of human polymorphonuclear leukocyte receptors for leukotriene B4. Identification of a subset of high affinity receptors that transduce the chemotactic response

J. Exp. Med.

AG-protein-coupled receptor for leukotriene B4 that mediates chemotaxis

Nature

Molecular and biological characterization of the murine leukotriene B4 receptor expressed on eosinophils

J. Exp. Med.

New members of the chemokine receptor gene family

J. Leukocyte Biol.

The molecular biology of leukocyte chemoattractant receptors

Annu. Rev. Immunol.

Second leukotriene B(4) receptor BLT2a new therapeutic target in inflammation and immunological disorders [see comments]

J. Exp. Med.

A novel hepatointestinal leukotriene B4 receptorcloning and functional characterization

J. Biol. Chem.

Molecular evolution of the human interleukin-8 receptor gene cluster

Nature Genet.

The in vitro and in vivo pharmacologic activity of the potent and selective leukotriene B4 receptor antagonist CP-105696

J. Pharmacol. Exp. Ther.

The preclinical pharmacological profile of the potent and selective leukotriene B4 antagonist CP-195543

J. Pharmacol. Exp. Ther.

Receptor antagonism of leukotriene B4 myotropic activity by the 26 disubstituted pyridine analog U-75302characterization on lung parenchyma strips

J. Lipid Mediat.

Leukotriene B4 receptor antagoniststhe ly255283 series of hydroxyacetophenones

J. Med. Chem.

BLT1 and BLT2: the leukotriene B₄ receptors

Main activities and pathophysiological roles of LTB₄

Assignment of LTB₄ activities to BLT1 and BLT2

Specific binding of leukotriene B₄ to receptors on human polymorphonuclear leukocytes

Heterogeneity of human polymorphonuclear leukocyte receptors for leukotriene B₄. Identification of a subset of high affinity receptors that transduce the chemotactic response

AG-protein-coupled receptor for leukotriene B₄ that mediates chemotaxis

Molecular and biological characterization of the murine leukotriene B₄ receptor expressed on eosinophils

A novel hepatointestinal leukotriene B₄ receptorcloning and functional characterization

The in vitro and in vivo pharmacologic activity of the potent and selective leukotriene B₄ receptor antagonist CP-105696

The preclinical pharmacological profile of the potent and selective leukotriene B₄ antagonist CP-195543

Receptor antagonism of leukotriene B₄ myotropic activity by the 26 disubstituted pyridine analog U-75302characterization on lung parenchyma strips

Leukotriene B₄ receptor antagoniststhe ly255283 series of hydroxyacetophenones