Trp-Lys-Tyr-Met-Val-Met stimulates phagocytosis via phospho-lipase D-dependent signaling in mouse dendritic cells

Lee, Ha-Young; Kang, Hyo-Jin; Jo, Eun Jin; Kim, Jung Im; Lee, Youl-Nam; Lee, Sang Hwa; Park, Yeong Min; Ryu, Sung Ho; Kwak, Jong‐Young; Bae, Yoe‐Sik

doi:10.1038/emm.2004.20

Cited by 25 publications

(21 citation statements)

References 26 publications

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“…Fpr3 expression in leukocytes has been discussed somewhat controversially in the past. Although one report detected low amounts of Fpr3 RNA in murine leukocytes (31), other studies failed to confirm this result despite the use of sensitive techniques such as RT-PCR (23,36,37). We thus carefully examined blood leukocytes for Fpr3 expression.…”

Section: Discussionmentioning

confidence: 97%

“…Conversely, careful quantitative PCR and in situ hybridization studies clearly showed that mouse Fpr3 mRNA is present in VSNs, but both studies found no evidence for an expression outside the olfactory system (23,24). So far, only a single report for the presence of low amounts of Fpr3 mRNA in Northern blots from murine leukocytes exists (31), but several other studies could not detect Fpr3 from blood samples (23), bone marrow (35), dendritic cells (36), or neutrophils (37), despite performing highly sensitive reverse transcriptasepolymerase chain reaction (RT-PCR) experiments. However, it is conceivable that Fpr3 protein is present in immune cells and that the failure to detect its expression can be attributed to low mRNA levels.…”

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confidence: 99%

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Strain-specific Loss of Formyl Peptide Receptor 3 in the Murine Vomeronasal and Immune Systems

Stempel¹,

Jung

Pérez-Gómez³

et al. 2016

Journal of Biological Chemistry

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Social animals benefit from sharing information that promotes fitness and survival (1-3). In rodents, there is extensive evidence that the detection of chemosensory cues emitted by other individuals is a fundamental feature of social recognition and a prerequisite for a wide range of social behaviors (4 -6).For example, rodents use such chemical signals to distinguish between parasitized individuals, recognize infected conspecifics, and avoid and display aversive responses to infected individuals (7-9). Defining the cellular and molecular mechanisms and neural circuits underlying the detection of infection-and illness-associated states is not only crucial for understanding the sensing of health status in animals but also for advancing our knowledge of disease-related odors and diagnostic olfactory biomarkers in humans (10, 11).The vomeronasal organ (VNO) 4 is an olfactory substructure of the mammalian nose that is essential for social recognition and chemical communication (12). The VNO houses vomeronasal sensory neurons (VSNs), specialized nerve cells that detect a wide range of volatile and non-volatile molecular cues, including pheromones and predator odors (13-15). Among these cues are major histocompatibility complex class I binding peptides (antigens) and other small urinary peptides (16 -18) thus providing initial support for an evolutionary link between recognition mechanisms in immune cells and subsets of VSNs (14, 19). More recently, clear evidence has emerged that the VNO plays an important role in mediating sick conspecific avoidance and thus seems to function as a sensor of infection (20), but the underlying cellular and molecular basis for this function remains unclear. VSNs are characterized by the expression of large families of G protein-coupled receptors, vomeronasal type 1 receptors (Vmn1r) expressed in the apical vomeronasal layer and vomeronasal type 2 receptor (Vmn2r) that function together with non-classical class I major histocompatibility complex receptors of the H2-Mv subtype in the basal layer (21, 22). An important development has been the identification of a third family of G protein-coupled receptors expressed in subsets of VSNs as follows: the formyl peptide receptors (Fprs) (23,24). Fprs are primarily known from the innate immune system where they are involved in chemoattraction of phagocytic immune cells to sites of infection mediating host defense against invading microorganisms (25-28). Fprs detect a wide range of inflammation markers as well as bacterial and mitochondrial peptides (25-28), and consistent with the results from immune cells, some of these ligands have also been shown to activate specific VSNs (23,29). Hence, members of the Fpr family are currently prime candidates for mediating VNO pathogen sensing, although it cannot be ruled out that

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Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 99%

Strain-specific Loss of Formyl Peptide Receptor 3 in the Murine Vomeronasal and Immune Systems

Stempel¹,

Jung

Pérez-Gómez³

et al. 2016

Journal of Biological Chemistry

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“…Fpr and ALX have also been identified in liver. ALX, but not Fpr or Fpr2, has been reported in heart (7,13,24,34). In this study, we test which of the eight mouse FPR gene family members encodes a receptor for F2L.…”

Section: F Ormylpeptide Receptor (Fpr)mentioning

confidence: 95%

F2L, a Peptide Derived from Heme-Binding Protein, Chemoattracts Mouse Neutrophils by Specifically Activating Fpr2, the Low-Affinity N-Formylpeptide Receptor

Gao

Guillabert

et al. 2007

The Journal of Immunology

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F2L (formylpeptide receptor (FPR)-like (FPRL)-2 ligand), a highly conserved acetylated peptide derived from the amino-terminal cleavage of heme-binding protein, is a potent chemoattractant for human monocytes and dendritic cells, and inhibits LPS-induced human dendritic cell maturation. We recently reported that F2L is able to activate the human receptors FPRL-1 and FPRL2, two members of the FPR family, with highest selectivity and affinity for FPRL2. To facilitate delineation of mechanisms of F2L action in vivo, we have now attempted to define its mouse receptors. This is complicated by the nonequivalence of the human and mouse FPR gene families (three vs at least eight members, respectively). When cell lines were transfected with plasmids encoding the eight mouse receptors, only the one expressing the receptor Fpr2 responded to F2L (EC50 ∼400 nM for both human and mouse F2L in both calcium flux and cAMP inhibition assays). This value is similar to F2L potency at human FPRL1. Consistent with this, mouse neutrophils, which like macrophages and dendritic cells express Fpr2, responded to human and mouse F2L in both calcium flux and chemotaxis assays with EC50 values similar to those found for Fpr2-expressing cell lines (∼500 nM). Moreover, neutrophils from mice genetically deficient in Fpr2 failed to respond to F2L. Thus, Fpr2 is a mouse receptor for F2L, and can be targeted for the study of F2L action in mouse models.

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“…mFPR2 can be activated by several peptide agonists for FPR2 [8][9][10]. mFPR2 has been detected in neutrophils, dendritic cells, microglia and astrocytes [9,11,12 erties under different conditions [13,14]. The expression of mFPR2 in microglia is enhanced by a variety of inflammatory stimulants, such as TNFα, interferon γ and ligands for TLR2, 3, 4, 7, 9 [12, 15-19].…”

Section: Introductionmentioning

confidence: 99%

Proinflammatory Stimulants Promote the Expression of a Promiscuous G Protein-Coupled Receptor, mFPR2, in Microvascular Endothelial Cells

Mou

Kong

et al. 2011

Inflammation

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Human formylpeptide receptor 2 (FPR2) and its mouse homologue mFPR2 belong to the G protein-coupled, seven-transmembrane receptor superfamily. Both FPR2 and mFPR2 recognize a variety of exogenous and host-derived chemotactic peptides associated with proinflammatory conditions. Since endothelial cells actively participate in inflammation, we investigated whether microvascular endothelial cells express mFPR2 and its regulation by proinflammatory factors. We found that resting primary mouse microvascular endothelial cells and a cell line bEnd.3 expressed low levels of mFPR2 at both mRNA and protein levels, which was markedly enhanced by two key proinflammatory stimulants, lipopolysaccharide (LPS) and interleukin (IL)-1β. While the inductive effect of LPS was dependent on the JNK MAP kinase, both JNK and ERK MAP kinases were utilized by IL-1β to enhance mFPR2 expression. Overexpression of dominant-negative IκBα attenuated LPS- and IL-1β-induced mFPR2 expression, indicating an essential role for NF-κB in regulating mFPR2 expression in endothelial cells by proinflammatory stimulants. Our results suggest that upregulated mFPR2 in vascular endothelial cells under inflammatory conditions may mediate cell responses in diseases in which mFPR2 agonists are elevated.

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Trp-Lys-Tyr-Met-Val-Met stimulates phagocytosis via phospho-lipase D-dependent signaling in mouse dendritic cells

Cited by 25 publications

References 26 publications

Strain-specific Loss of Formyl Peptide Receptor 3 in the Murine Vomeronasal and Immune Systems

Strain-specific Loss of Formyl Peptide Receptor 3 in the Murine Vomeronasal and Immune Systems

F2L, a Peptide Derived from Heme-Binding Protein, Chemoattracts Mouse Neutrophils by Specifically Activating Fpr2, the Low-Affinity N-Formylpeptide Receptor

Proinflammatory Stimulants Promote the Expression of a Promiscuous G Protein-Coupled Receptor, mFPR2, in Microvascular Endothelial Cells

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