scholarly journals Macrophages in Healing Wounds: Paradoxes and Paradigms

2021 ◽  
Vol 22 (2) ◽  
pp. 950
Author(s):  
Luisa A. DiPietro ◽  
Traci A. Wilgus ◽  
Timothy J. Koh
Keyword(s):  
Host Defense ◽  
Normal Skin ◽  
Skin Wounds ◽  
Apparent Paradox ◽  
Functional Attributes ◽  
New Information ◽  
Healing Wounds ◽  
Macrophage Phenotypes ◽  
Skin Healing ◽  
Adult Skin

Macrophages are prominent cells in normally healing adult skin wounds, yet their exact functions and functional significance to healing outcomes remain enigmatic. Many functional attributes are ascribed to wound macrophages, including host defense and support of the proliferation of new tissue to replace that lost by injury. Indeed, the depletion of macrophages is unmistakably detrimental to normal skin healing in adult mammals. Yet in certain systems, dermal wounds seem to heal well with limited or even no functional macrophages, creating an apparent paradox regarding the function of this cell in wounds. Recent advances in our understanding of wound macrophage phenotypes, along with new information about cellular plasticity in wounds, may provide some explanation for the apparently contradictory findings and suggest new paradigms regarding macrophage function in wounds. Continued study of this remarkable cell is needed to develop effective therapeutic options to improve healing outcomes.

scholarly journals Low-threshold mechanoreceptors play a frequency-dependent dual role in subjective ratings of mechanical allodynia

2017 ◽  
Vol 118 (6) ◽  
pp. 3360-3369 ◽  
Author(s):  
Line S. Löken ◽  
Eugene P. Duff ◽  
Irene Tracey
Keyword(s):  
Mechanical Allodynia ◽  
Brain Activity ◽  
Normal Skin ◽  
Dual Role ◽  
Apparent Paradox ◽  
Frequency Dependent ◽  
Firing Rates ◽  
Dynamic Mechanical ◽  
Gate Control Theory ◽  
Low Threshold

In the setting of injury, myelinated primary afferent fibers that normally signal light touch are thought to switch modality and instead signal pain. In the absence of injury, touch is perceived as more intense when firing rates of Aβ afferents increase. However, it is not known if varying the firing rates of Aβ afferents have any consequence to the perception of dynamic mechanical allodynia (DMA). We hypothesized that, in the setting of injury, the unpleasantness of DMA would be intensified as the firing rates of Aβ afferents increase. Using a stimulus-response protocol established in normal skin, where an increase in brush velocity results in an increase of Aβ afferent firing rates, we tested if brush velocity modulated the unpleasantness of capsaicin-induced DMA. We analyzed how changes in estimated low-threshold mechanoreceptor firing activity influenced perception and brain activity (functional MRI) of DMA. Brushing on normal skin was perceived as pleasant, but brushing on sensitized skin produced both painful and pleasant sensations. Surprisingly, there was an inverse relationship between Aβ firing rates and unpleasantness such that brush stimuli that produced low firing rates were most painful and those that elicited high firing rates were rated as pleasant. Concurrently to this, we found increased cortical activity in response to low Aβ firing rates in regions previously implicated in pain processing during brushing of sensitized skin, but not normal skin. We suggest that Aβ signals do not merely switch modality to signal pain during injury. Instead, they exert a high- and low-frequency-dependent dual role in the injured state, with respectively both pleasant and unpleasant consequences. NEW & NOTEWORTHY We suggest that Aβ signals do not simply switch modality to signal pain during injury but play a frequency-dependent and dual role in the injured state with both pleasant and unpleasant consequences. These results provide a framework to resolve the apparent paradox of how touch can inhibit pain, as proposed by the Gate Control Theory and the existence of dynamic mechanical allodynia.

[3H]Fucose incorporation by healing skin wounds and the effect of transglutaminase inhibitors

1982 ◽  
Vol 60 (8) ◽  
pp. 777-781 ◽  
Author(s):  
J. Michael Bowness
Keyword(s):  
Sequential Extraction ◽  
Specific Activity ◽  
Dry Weight ◽  
Insoluble Residue ◽  
Skin Wounds ◽  
Salt Solutions ◽  
Healing Wounds ◽  
Made In

Punch wounds (3 mm) were made in the skin of rats and the animals were killed after 1 or 3 days. Plugs (4 mm) of wounded and unwounded skin were incubated in vitro with [3H]fucose. The labelled plugs were homogenized and subjected to sequential extraction with buffered salt solutions, ethanol–ether, and 8 M urea – 50 mM dithiothreitol (DTT). Nondialysable counts in the extracts and insoluble residue were determined and the incorporation of label by wounded and unwounded skin plugs was compared. Wound plugs showed a greater total incorporation of [3H]fucose. In addition, a greater proportion of [3H]fucose was found in the urea–DTT extracts. The highest specific activity (disintegrations per minute t [3H]fucose per milligram dry weight) was found in a finely dispersed precipitate, sedimenting at 10 000 × g but not at 1000 × g. The transglutaminase inhibitors aminoacetonitrile and dansyl cadaverine were found to increase the extractability of a portion of the material which incorporated [3H]fucose without affecting the total incorporation. These results show that healing wounds have an increased biosynthetic capacity for an insoluble fucosylated glycoprotein fraction and they suggest that transglutaminase is necessary to make this fraction fully insoluble.

scholarly journals Induction of tenascin in healing wounds.

1988 ◽  
Vol 107 (6) ◽  
pp. 2757-2767 ◽  
Author(s):  
E J Mackie ◽  
W Halfter ◽  
D Liverani
Keyword(s):  
Extracellular Matrix ◽  
Normal Skin ◽  
Basement Membranes ◽  
Regulatory Mechanisms ◽  
Wound Edge ◽  
Cut Edge ◽  
Cultured Skin ◽  
The Matrix ◽  
Skin Explants ◽  
Healing Wounds

The distribution of the extracellular matrix glycoprotein, tenascin, in normal skin and healing skin wounds in rats, has been investigated by immunohistochemistry. In normal skin, tenascin was sparsely distributed, predominantly in association with basement membranes. In wounds, there was a marked increase in the expression of tenascin at the wound edge in all levels of the skin. There was also particularly strong tenascin staining at the dermal-epidermal junction beneath migrating, proliferating epidermis. Tenascin was present throughout the matrix of the granulation tissue, which filled full-thickness wounds, but was not detectable in the scar after wound contraction was complete. The distribution of tenascin was spatially and temporally different from that of fibronectin, and tenascin appeared before laminin beneath migrating epidermis. Tenascin was not entirely codistributed with myofibroblasts, the contractile wound fibroblasts. In EM studies of wounds, tenascin was localized in the basal lamina at the dermal-epidermal junction, as well as in the extracellular matrix of the adjacent dermal stroma, where it was either distributed homogeneously or bound to the surface of collagen fibers. In cultured skin explants, in which epidermis migrated over the cut edge of the dermis, tenascin, but not fibronectin, appeared in the dermis underlying the migrating epithelium. This demonstrates that migrating, proliferating epidermis induces the production of tenascin. The results presented here suggest that tenascin is important in wound healing and is subject to quite different regulatory mechanisms than is fibronectin.

STUDIES ON THE TURN-OVER OF SIMULTANEOUSLY INJECTED GUINEA-PIG ALBUMIN-125I AND THYROXINE-131I IN SKIN, WOUNDS AND LIVER OF GUINEA PIGS

1964 ◽  
Vol 47 (3) ◽  
pp. 402-408
Author(s):  
Erik Moltke ◽  
Hans Funch-Rosenberg ◽  
Heinz J. M. Hansen
Keyword(s):  
Guinea Pig ◽  
Guinea Pigs ◽  
Normal Skin ◽  
Experimental Period ◽  
Skin Wounds ◽  
High Uptake ◽  
Albumin Ratio ◽  
Albumin Content ◽  
Turn Over ◽  
Very High

ABSTRACT The distribution of simultaneously injected 125I-labelled guinea-pig albumin and 131I-labelled thyroxine in the skin, skin-wounds and liver of guinea-pigs has been investigated. In the plasma albumin was retained in larger amounts than thyroxine but the activities decreased from 2–24 hours after the injection (h. p. i.) at exactly the same rate. In the liver the uptake of thyroxine was considerably higher than that of albumin, but both decreased at the same rate as in the plasma. In the skin thyroxine was also taken up in relatively larger amounts than albumin at 2 and 6 h. p. i.; thyroxine decreased at the same rate as in the plasma, while the uptake of albumin increased. In 7-day wounds the thyroxine content was only a little higher than in normal skin at 2 h. p. i. while the albumin content had markedly increased; thyroxine decreased and albumin increased at the same rates as in skin. Fresh wounds showed a very high uptake of both albumin and thyroxine with no decrease from 2–24 h. p. i.; the relation between the amounts was close to – but significantly different from – that seen in plasma. The results clearly indicate that albumin and thyroxine move quite independently of each other in skin, old skin-wounds and liver. In fresh wounds, however, there is a constant thyroxine-albumin ratio during the experimental period.

EFFECT OF THYROIDECTOMY AND THYROXINE ON THE MUCOPOLYSACCHARIDES OF WOUNDS AND SKIN

1960 ◽  
Vol XXXIV (III) ◽  
pp. 407-410 ◽  
Author(s):  
Erik Moltke ◽  
lb Lorenzen
Keyword(s):  
Guinea Pigs ◽  
Normal Skin ◽  
Total Content ◽  
Skin Wounds ◽  
Rapid Synthesis ◽  
Acid Mucopolysaccharides ◽  
And Control ◽  
Hexosamine Content

ABSTRACT The incorporation of 35S sulphate and the total content of hexosamine in skin wounds was determined in thyroidectomized, normal, and thyroxine-treated guinea pigs. Seven days after the production of the wounds, all three groups showed an increase in the 35S incorporation and in the hexosamine content as compared with normal skin. While the relative incorporation of 35S sulphate was most intense among thyroidectomized guinea pigs, the three groups showed no difference in the content of hexosamine. Thyroidectomy induced a more rapid synthesis of sulphated mucopolysaccharide than that observed in the thyroxine-treated and control guinea pigs, whereas the total content of acid mucopolysaccharides in the wound tissues was not affected by either thyroidectomy or thyroxine.

scholarly journals Identification of Novel Molecular Markers of Human Th17 Cells

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1611 ◽  
Author(s):  
Anna Sałkowska ◽  
Kaja Karaś ◽  
Iwona Karwaciak ◽  
Aurelia Walczak-Drzewiecka ◽  
Mariusz Krawczyk ◽  
...  
Keyword(s):  
Host Defense ◽  
Th17 Cell ◽  
Th17 Cells ◽  
Cathepsin L ◽  
Cell Type ◽  
Protein Levels ◽  
Pathological Conditions ◽  
Th17 Lymphocytes ◽  
New Information ◽  
Apolipoprotein D

Th17 cells are important players in host defense against pathogens such as Staphylococcus aureus, Candida albicans, and Bacillus anthracis. Th17 cell-mediated inflammation, under certain conditions in which balance in the immune system is disrupted, is the underlying pathogenic mechanism of certain autoimmune disorders, e.g., rheumatoid arthritis, Graves’ disease, multiple sclerosis, and psoriasis. In the present study, using transcriptomic profiling, we selected genes and analyzed the expression of these genes to find potential novel markers of Th17 lymphocytes. We found that APOD (apolipoprotein D); C1QL1 (complement component 1, Q subcomponent-like protein 1); and CTSL (cathepsin L) are expressed at significantly higher mRNA and protein levels in Th17 cells than in the Th1, Th2, and Treg subtypes. Interestingly, these genes and the proteins they encode are well associated with the function of Th17 cells, as these cells produce inflammation, which is linked with atherosclerosis and angiogenesis. Furthermore, we found that high expression of these genes in Th17 cells is associated with the acetylation of H2BK12 within their promoters. Thus, our results provide new information regarding this cell type. Based on these results, we also hope to better identify pathological conditions of clinical significance caused by Th17 cells.

scholarly journals TREATMENT OF PROBLEMATIC SKIN WOUNDS BASED ON THE PLATELET-RICH PLASMA METHOD. OUR OWN ALGORITHMS FOR APPLICATION

2020 ◽  
Vol 26 (4) ◽  
pp. 3436-3442
Author(s):  
Tsvetan Sokolov ◽  
◽  
Anelya Manukova ◽  
Vihar Kovachev ◽  
Mancho Kovachev ◽  
...  
Keyword(s):  
Platelet Rich Plasma ◽  
Skin Wounds ◽  
Plasma Method ◽  
Normal Life ◽  
Complicated Skin ◽  
Prevention And Treatment ◽  
Skin Healing

OBJECTIVE: The objective of this paper is to present the application of our own algorithms for prevention and treatment of problematic skin wounds (PSW) by using the platelet-rich plasma (PRP) based on the first study on PRP application carried out in Bulgaria. MATERIAL AND METHODS: The study was carried out at the Clinic of Orthopedics and Traumatology, UMBAL Kanev Ruse, for a period of 84 months - from February 2009 to September 2016. A total of 83 patients with PSW have been treated with platelet-rich plasma. Scores introduced by Cancela AM are used for the assessment of the respective wound. Each of these scores is used for assessing specific wound parameters. RESULTS: Our own algorithms for prevention and treatment of PSW by PRP increase the percentage of successfully cured wounds. Prevention algorithm of applying PRP ensures that a high percentage of acute skin wounds will not turn into PSW. The proposed algorithms for prevention and treatment of PSW by applying PRP are an effective and safe way to reduce the uncured complicated skin wounds and ensure the subsequent normal life of patients. They also ensure more predictable skin healing. CONCLUSION: Our own algorithms for prevention and treatment of PSW by PRP increase the percentage of successfully cured wounds. The proposed algorithms for prevention and treatment of PSW by applying PRP are an effective and safe way to reduce the uncured complicated skin wounds and ensure the subsequent normal life of patients.

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