MRGPR-mediated activation of local mast cells clears cutaneous bacterial infection and protects against reinfection

Arifuzzaman, Mohammad; Mobley, Yuvon Rondreise; Choi, Hae Woong; Bist, Pradeep; Salinas, Cristina A.; Brown, Zachary D.; Chen, Swaine L.; Staats, Herman F.; Abraham, Soman N.

doi:10.1126/sciadv.aav0216

Cited by 90 publications

(95 citation statements)

References 51 publications

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“…Poor wound healing after extensive burn, severe traumatic injury, surgery, or chronic diseases such as diabetes remains a challenging clinical problem that leads to low quality of life, substantial healthy cost, and high mortality (2,3). Open, moist, and exuding wound provides a perfect environment for bacterial colonization, and bacterial infection is recognized as a major factor that delays the healing process of wound (4,5). The host's inflammatory response is a local protective reaction in response to injury and essential for infection control in the wound sites (3).…”

Section: Introductionmentioning

confidence: 99%

Ångstrom-scale silver particle–embedded carbomer gel promotes wound healing by inhibiting bacterial colonization and inflammation

et al. 2020

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Poor wound healing after diabetes or extensive burn remains a challenging problem. Recently, we presented a physical approach to fabricate ultrasmall silver particles from Ångstrom scale to nanoscale and determined the antitumor efficacy of Ångstrom-scale silver particles (AgÅPs) in the smallest size range. Here we used the medium-sized AgÅPs (65.9 ± 31.6 Å) to prepare carbomer gel incorporated with these larger AgÅPs (L-AgÅPs-gel) and demonstrated the potent broad-spectrum antibacterial activity of L-AgÅPs-gel without obvious toxicity on wound healing–related cells. Induction of reactive oxygen species contributed to L-AgÅPs-gel–induced bacterial death. Topical application of L-AgÅPs-gel to mouse skin triggered much stronger effects than the commercial silver nanoparticles (AgNPs)–gel to prevent bacterial colonization, reduce inflammation, and accelerate diabetic and burn wound healing. L-AgÅPs were distributed locally in skin without inducing systemic toxicities. This study suggests that L-AgÅPs-gel represents an effective and safe antibacterial and anti-inflammatory material for wound therapy.

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Section: Introductionmentioning

confidence: 99%

Ångstrom-scale silver particle–embedded carbomer gel promotes wound healing by inhibiting bacterial colonization and inflammation

et al. 2020

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“…Mast cell activators can promote survival in several animal models of infection. Arifuzzaman et al found that mastoparan, a small peptide derived from wasp venom that activates mast cells through the MRGPRX2 receptor, was able to enhance clearance of Staphylococcus aureus in a mouse model of skin infection [59]. Activation of mast cells after infection was able to drive neutrophil recruitment to the site of infection, enhancing clearance of bacteria from and healing of the infected skin lesion.…”

Section: Mast Cell Activators Used To Treat Infectionmentioning

confidence: 99%

Harnessing the Power of Mast Cells in Unconventional Immunotherapy Strategies and Vaccine Adjuvants

Willows

Kulka

2020

Preprint

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Mast cells are long-lived, granular, myeloid-derived leukocytes that have significant protective and repair functions in tissues. Mast cells sense disruptions in the local microenvironment and are first responders to physical, chemical and biological insults. When activated, mast cells release growth factors, proteases, chemotactic proteins and cytokines thereby mobilizing and amplifying the innate and adaptive immune system. Mast cells are therefore significant regulators of homeostatic functions and may be essential in microenvironmental changes during pathogen invasion and disease. During infection by helminths, bacteria and viruses, mast cells release antimicrobial factors to facilitate pathogen expulsion and eradication. Mast cell-derived proteases and growth factors protect tissues from insect/snake bites and exposure to ultraviolet radiation. Finally, mast cells release mediators that promote wound healing in the inflammatory, proliferative and remodeling stages. Since mast cells have such a powerful repertoire of functions, targeting mast cells may be an effective new strategy for immunotherapy of disease and design of novel vaccine adjuvants. In this review, we will examine how certain strategies that specifically target and activate mast cells can be used to treat and resolve infections, augment vaccines and heal wounds. Although these strategies may be protective in certain circumstances, mast cells activation may be deleterious if not carefully controlled and any therapeutic strategy using mast cell activators must be carefully explored.

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“…Wasp venom is mainly composed of a few biological active peptides (like mast cell degranulating peptides and mastoparan) (Argiolas and Pisano, 1985 ; Monteiro et al, 2009 ), active enzymes (phospholipase A2 and hyaluronidase) (Tsai et al, 2011 ), histamine, 5-hydroxytryptamine, choline, glycerin, amino acids, and so on (Schmidt, 1982 ). Among them, peptides in the wasp venom usually exhibit superior pharmacological effects and a promising clinical value (Arifuzzaman et al, 2019 ; Li et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Advances in the Study of Structural Modification and Biological Activities of Anoplin

Huang

Jin

et al. 2020

Front. Chem.

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Anoplin is an amphipathic, α-helical bioactive peptide from wasp venom. In recent years, pharmaceutical and organic chemists discovered that anoplin and its derivatives showed multiple pharmacological activities in antibacterial, antitumor, antifungal, and antimalarial activities. Owing to the simple and unique structure and diverse biological activities, anoplin has attracted considerable research interests. This review highlights the advances in structural modification, biological activities, and the outlook of anoplin in order to provide a basis for new drug design and delivery.

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MRGPR-mediated activation of local mast cells clears cutaneous bacterial infection and protects against reinfection

Abstract: Selective activation of local mast cells promotes healing of bacterial skin infections and protects against reinfection.

Cited by 90 publications

References 51 publications

Ångstrom-scale silver particle–embedded carbomer gel promotes wound healing by inhibiting bacterial colonization and inflammation

Ångstrom-scale silver particle–embedded carbomer gel promotes wound healing by inhibiting bacterial colonization and inflammation

Harnessing the Power of Mast Cells in Unconventional Immunotherapy Strategies and Vaccine Adjuvants

Advances in the Study of Structural Modification and Biological Activities of Anoplin

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