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Study · Animal study (in vivo) · mouse · 2021

8 results

Murepavadin, a Small Molecule Host Defense Peptide Mimetic, Activates Mast Cells via MRGPRX2 and MrgprB2.

Amponnawarat A, Chompunud Na Ayudhya C, Ali H

Frontiers in immunology23 Jun 2021Cited by 24 (Europe PMC)

PMID34248979 (opens in a new tab)PMCIDPMC8261236 (opens in a new tab)DOI10.3389/fimmu.2021.689410 (opens in a new tab)PepBankPUB-34248979
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Summary

Pseudomonas aeruginosa is a frequent cause of hospital-acquired wound infection and is difficult to treat because it forms biofilms and displays antibiotic resistance. Previous studies in mice demonstrated that mast cells (MCs) not only contribute to P. aeruginosa eradication but also promote wound healing via an unknown mechanism. We recently reported that host defense peptides (HDPs) induce human MC degranulation via Mas-related G protein-coupled receptor-X2 (MRGPRX2). Small molecule HDP mimetics have distinct advantages over HDPs because they are inexpensive to synthesize and display high stability, bioavailability, and low toxicity. Murepavadin is a lipidated HDP mimetic, (also known as POL7080), which displays antibacterial activity against a broad panel of multi-drug-resistant P. aeruginosa. We found that murepavadin induces Ca2+ mobilization, degranulation, chemokine IL-8 and CCL3 production in a human MC line (LAD2 cells) endogenously expressing MRGPRX2. Murepavadin also caused degranulation in RBL-2H3 cells expressing MRGPRX2 but this response was significantly reduced in cells expressing missense variants within the receptor's ligand binding (G165E) or G protein coupling (V282M) domains. Compound 48/80 induced β-arrestin recruitment and promoted receptor internalization, which resulted in substantial decrease in the subsequent responsiveness to the MRGPRX2 agonist. By contrast, murepavadin did not cause β-arrestin-mediated MRGPRX2 regulation. Murepavadin induced degranulation in mouse peritoneal MCs via MrgprB2 (ortholog of human MRGPRX2) and caused increased vascular permeability in wild-type mice but not in MrgprB2-/- mice. The data presented herein demonstrate that murepavadin activates human MCs via MRGPRX2 and murine MCs via MrgprB2 and that MRGPRX2 is resistant to β-arrestin-mediated receptor regulation. Thus, besides its direct activity against P. aeruginosa, murepavadin may contribute to bacterial clearance and promote wound healing by harnessing MC's immunomodulatory property via the activation of MRGPRX2.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study8

8 results from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Mechanism

    In mice, murepavadin increased vascular permeability in wild-type mice but not in MrgprB2 knockout mice.

    In plain wordsIn mice, murepavadin increased vascular permeability in wild-type mice but not in mice without MrgprB2.

    Peptide
    Murepavadin
    Outcome
    MixedVascular permeability
    Study

    mousen: not reported in source

    Wild-type and MrgprB2 knockout mice
    Outcome group
    Receptor activity and mechanism · Immune and inflammation
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Murepavadin induced degranulation in mouse peritoneal MCs via MrgprB2 (ortholog of human MRGPRX2) and caused increased vascular permeability in wild-type mice but not in MrgprB2-/- mice.
  2. 02LabEx vivo tissueMechanism

    In mouse peritoneal mast cells, murepavadin induced degranulation via MrgprB2.

    In plain wordsIn lab tests, murepavadin induced mouse mast cell degranulation through MrgprB2.

    Peptide
    Murepavadin
    Outcome
    IncreasePeritoneal mast cell degranulation
    Study

    mousen: not reported in source

    Peritoneal mast cells
    Outcome group
    Receptor activity and mechanism · Immune and inflammation
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Murepavadin induced degranulation in mouse peritoneal MCs via MrgprB2 (ortholog of human MRGPRX2) and caused increased vascular permeability in wild-type mice but not in MrgprB2-/- mice.
  3. 03LabIn vitro (cells)Mechanism

    In human LAD2 mast cells, murepavadin induced calcium mobilization.

    In plain wordsIn cells, murepavadin induced calcium mobilization.

    Peptide
    Murepavadin
    Outcome
    IncreaseCalcium mobilization
    Study

    humann: not reported in source

    LAD2 mast cells
    Outcome group
    Receptor activity and mechanism · Immune and inflammation
    Studied dose
    Dose not stated

    Source sentences

    Summary
    We found that murepavadin induces Ca2+ mobilization, degranulation, chemokine IL-8 and CCL3 production in a human MC line (LAD2 cells) endogenously expressing MRGPRX2.
  4. 04LabIn vitro (cells)Mechanism

    In human LAD2 mast cells, murepavadin induced degranulation.

    In plain wordsIn cells, murepavadin induced mast cell degranulation.

    Peptide
    Murepavadin
    Outcome
    IncreaseLAD2 degranulation
    Study

    humann: not reported in source

    LAD2 mast cells
    Outcome group
    Receptor activity and mechanism · Immune and inflammation
    Studied dose
    Dose not stated

    Source sentences

    Summary
    We found that murepavadin induces Ca2+ mobilization, degranulation, chemokine IL-8 and CCL3 production in a human MC line (LAD2 cells) endogenously expressing MRGPRX2.
  5. 05LabIn vitro (cells)Mechanism

    In human LAD2 mast cells, murepavadin induced IL-8 production.

    In plain wordsIn cells, murepavadin induced IL-8 production.

    Peptide
    Murepavadin
    Outcome
    IncreaseIL-8 production
    Study

    humann: not reported in source

    LAD2 mast cells
    Outcome group
    Receptor activity and mechanism · Immune and inflammation
    Studied dose
    Dose not stated

    Source sentences

    Summary
    We found that murepavadin induces Ca2+ mobilization, degranulation, chemokine IL-8 and CCL3 production in a human MC line (LAD2 cells) endogenously expressing MRGPRX2.
  6. 06LabIn vitro (cells)Mechanism

    In human LAD2 mast cells, murepavadin induced CCL3 production.

    In plain wordsIn cells, murepavadin induced CCL3 production.

    Peptide
    Murepavadin
    Outcome
    IncreaseCCL3 production
    Study

    humann: not reported in source

    LAD2 mast cells
    Outcome group
    Receptor activity and mechanism · Immune and inflammation
    Studied dose
    Dose not stated

    Source sentences

    Summary
    We found that murepavadin induces Ca2+ mobilization, degranulation, chemokine IL-8 and CCL3 production in a human MC line (LAD2 cells) endogenously expressing MRGPRX2.
  7. 07LabIn vitro (cells)Mechanism

    In RBL-2H3 cells expressing MRGPRX2, murepavadin caused degranulation, with reduced responses in receptor missense variants.

    In plain wordsIn cells, murepavadin caused degranulation, with smaller responses in cells with receptor variants.

    Peptide
    Murepavadin
    Outcome
    IncreaseRBL-2H3 degranulation
    Study

    n: not reported in source

    RBL-2H3 cells expressing MRGPRX2
    Outcome group
    Receptor activity and mechanism · Immune and inflammation
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Murepavadin also caused degranulation in RBL-2H3 cells expressing MRGPRX2 but this response was significantly reduced in cells expressing missense variants within the receptor's ligand binding (G165E) or G protein coupling (V282M) domains.
  8. 08LabIn vitro (cells)Mechanism

    In mast cell experiments, murepavadin did not cause beta-arrestin-mediated MRGPRX2 regulation.

    In plain wordsIn cells, murepavadin did not cause beta-arrestin-mediated receptor regulation.

    Peptide
    Murepavadin
    Outcome
    No significant changeBeta-arrestin-mediated MRGPRX2 regulation
    Study

    n: not reported in source

    Mast cell experiments
    Outcome group
    Receptor activity and mechanism · Immune and inflammation
    Studied dose
    Dose not stated

    Source sentences

    Summary
    By contrast, murepavadin did not cause β-arrestin-mediated MRGPRX2 regulation.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    27 Oct 2026, 18:20 UTC

    Study results updated

  2. Version 1

    27 Oct 2026, 16:32 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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