Immune Cells in Cutaneous Wound Healing: A Review of Functional Data from Animal Models

Chesko, David M.; Wilgus, Traci A.

doi:10.3390/ijms23052444

Cited by 18 publications

(17 citation statements)

References 96 publications

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“…NK cells, via their cytotoxic activity, might participate in this apoptotic phase by killing overstimulated macrophages ( 8 , 43 ) and neutrophils ( 47 ). Algosteril, by increasing NK cell cytotoxic and immune-modulatory activities, may thus participate not only in the enhancement of local defense but also in the resolution of the inflammatory phase, thus enabling the activation of the next phase of healing, namely granulation ( 16 , 48 , 49 ).…”

Section: Discussionmentioning

confidence: 99%

Modulation of NK cell activation by exogenous calcium from alginate dressings in vitro

et al. 2023

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Natural Killer (NK) cells participate in the defense against infection by killing pathogens and infected cells and secreting immuno-modulatory cytokines. Defects in NK cell activity have been reported in obese, diabetic, and elderly patients that are at high risk of developing infected chronic wounds. Calcium alginate dressings are indicated for the debridement during the inflammatory phase of healing. Since calcium ions are major activators of NK cells, we hypothesized that these dressings could enhance NK functions, as investigated in vitro herein. Primary human blood NK cells were freshly-isolated from healthy volunteers and exposed to conditioned media (CM) from two alginate dressings, Algosteril® (ALG, pure Ca2+ alginate) and Biatain® Alginate (BIA, Ca2+ alginate with CMC), in comparison with an exogenous 3mM calcium solution. Our results demonstrated that exogenous calcium and ALG-CM, but not BIA-CM, induced NK cell activation and enhanced their capacity to kill their targets as a result of increased degranulation. NK cell stimulation by ALG depended on the influx of extracellular Ca2+via the SOCE Ca2+ permeable plasma membrane channels. ALG-CM also activated NK cell cytokine production of IFN-γ and TNF-α through a partly Ca2+-independent mechanism. This work highlights the non-equivalence between alginate dressings for NK cell stimulation and shows that the pure calcium alginate dressing Algosteril® enhances NK cell cytotoxic and immuno-modulatory activities. Altogether, these results underline a specific property of this medical device in innate defense that is key for the cutaneous wound healing process.

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Section: Discussionmentioning

confidence: 99%

Modulation of NK cell activation by exogenous calcium from alginate dressings in vitro

et al. 2023

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“…In the absence of platelets, mediators produced by other cells could overcome the lack of platelet-derived mediators in thrombocytopenic mice. [ 19 ] Dimitra Gialamprinou thought that prostaglandin E1 synthesis modulated by platelets affected hypersensitive response. [ 20 ]…”

Section: Resultsmentioning

confidence: 99%

The role of platelets in central hubs of inflammation: A literature review

Bo,

Lu,

et al. 2024

Medicine

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Platelets are increasingly recognized for their multifaceted roles in inflammation beyond their traditional involvement in haemostasis. This review consolidates knowledge on platelets as critical players in inflammatory responses. This study did an extensive search of electronic databases and identified studies on platelets in inflammation, focusing on molecular mechanisms, cell interactions, and clinical implications, emphasizing recent publications. Platelets contribute to inflammation via surface receptors, release of mediators, and participation in neutrophil extracellular trap formation. They are implicated in diseases like atherosclerosis, rheumatoid arthritis, and sepsis, highlighting their interaction with immune cells as pivotal in the onset and resolution of inflammation. Platelets are central to regulating inflammation, offering new therapeutic targets for inflammatory diseases. Future research should explore specific molecular pathways of platelets in inflammation for therapeutic intervention.

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“…66 Due to the complex nature of wound healing, a number of cell types play important roles during the wound healing process. [67][68][69] Here, we report that miR-409-3p, an anti-angiomiR, significantly modulates EC-driven angiogenic processes and stimulates wound healing in response to hyperglycemia. To bifurcate potential contribution from other cell types, we measured M1 and M2 macrophage markers by RT-qPCR and found no difference in their expression in the MiR409 Ind-ECKO group compared to the MiR409 fl/fl control group (Figure S6).…”

Section: F I G U R Ementioning

confidence: 85%

“…Due to the complex nature of wound healing, a number of cell types play important roles during the wound healing process 67–69 . Here, we report that miR‐409‐3p, an anti‐angiomiR, significantly modulates EC‐driven angiogenic processes and stimulates wound healing in response to hyperglycemia.…”

Section: Discussionmentioning

confidence: 98%

MicroRNA‐409‐3p/BTG2 signaling axis improves impaired angiogenesis and wound healing in obese mice

Bestepe,

Ghanem,

Fritsche

et al. 2024

The FASEB Journal

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Wound healing is facilitated by neoangiogenesis, a complex process that is essential to tissue repair in response to injury. MicroRNAs are small, noncoding RNAs that can regulate the wound healing process including stimulation of impaired angiogenesis that is associated with type‐2 diabetes (T2D). Expression of miR‐409‐3p was significantly increased in the nonhealing skin wounds of patients with T2D compared to the non‐wounded normal skin, and in the skin of a murine model with T2D. In response to high glucose, neutralization of miR‐409‐3p markedly improved EC growth and migration in human umbilical vein endothelial cells (HUVECs), promoted wound closure and angiogenesis as measured by increased CD31 in human skin organoids, while overexpression attenuated EC angiogenic responses. Bulk mRNA‐Seq transcriptomic profiling revealed BTG2 as a target of miR‐409‐3p, where overexpression of miR‐409‐3p significantly decreased BTG2 mRNA and protein expression. A 3′ untranslated region (3′‐UTR) luciferase assay of BTG2 revealed decreased luciferase activity with overexpression of miR‐409‐3p, while inhibition had opposite effects. Mechanistically, in response to high glucose, miR‐409‐3p deficiency in ECs resulted in increased mTOR phosphorylation, meanwhile BTG‐anti‐proliferation factor 2 (BTG2) silencing significantly decreased mTOR phosphorylation. Endothelial‐specific and tamoxifen‐inducible miR‐409‐3p knockout mice (MiR‐409IndECKO) with hyperglycemia that underwent dorsal skin wounding showed significant improvement of wound closure, increased blood flow, granulation tissue thickness (GTT), and CD31 that correlated with increased BTG2 expression. Taken together, our results show that miR‐409‐3p is a critical mediator of impaired angiogenesis in diabetic skin wound healing.

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Immune Cells in Cutaneous Wound Healing: A Review of Functional Data from Animal Models

Cited by 18 publications

References 96 publications

Modulation of NK cell activation by exogenous calcium from alginate dressings in vitro

Modulation of NK cell activation by exogenous calcium from alginate dressings in vitro

The role of platelets in central hubs of inflammation: A literature review

MicroRNA‐409‐3p/BTG2 signaling axis improves impaired angiogenesis and wound healing in obese mice

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