scholarly journals Mast cells are critical for controlling the bacterial burden and the healing of infected wounds

2019 ◽  
Vol 116 (41) ◽  
pp. 20500-20504 ◽  
Author(s):  
C. Zimmermann ◽  
D. Troeltzsch ◽  
V. A. Giménez-Rivera ◽  
S. J. Galli ◽  
M. Metz ◽  
...  
Keyword(s):  
Mast Cells ◽  
Wound Infection ◽  
Bacterial Infections ◽  
Wound Closure ◽  
Defense Mechanism ◽  
Defense Responses ◽  
Skin Wound ◽  
Mouse Strains ◽  
Bacterial Clearance ◽  
Bacterial Killing

Skin wound infections are a significant health problem, and antibiotic resistance is on the rise. Mast cells (MCs) have been shown to contribute to host–defense responses in certain bacterial infections, but their role in skin wound superinfection is unknown. We subjected 2 MC-deficient mouse strains to Pseudomonas aeruginosa skin wound infection and found significantly delayed wound closure in infected skin wounds. This delay was associated with impaired bacterial clearance in the absence of MCs. Engraftment of MCs restored both bacterial clearance and wound closure. Bacterial killing was dependent on IL-6 released from MCs, and engraftment with IL-6–deficient MCs failed to control wound infection. Treatment with recombinant IL-6 enhanced bacterial killing and resulted in the control of wound infection and normal wound healing in vivo. Taken together, our results demonstrate a defense mechanism for boosting host innate immune responses, namely effects of MC-derived IL-6 on antimicrobial functions of keratinocytes.

scholarly journals Differential effects of gram-positive and gram-negative bacterial products on morphine induced inhibition of phagocytosis

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Jana Ninkovic ◽  
Vidhu Anand ◽  
Raini Dutta ◽  
Li Zhang ◽  
Anuj Saluja ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Drug Abusers ◽  
Bacterial Clearance ◽  
Chronic Morphine ◽  
Gram Positive ◽  
Bacterial Killing ◽  
Differential Effects ◽  
Secondary Infections ◽  
First Time ◽  
Dependent Signaling Pathway

Abstract Opioid drug abusers have a greater susceptibility to gram positive (Gram (+)) bacterial infections. However, the mechanism underlying opioid modulation of Gram (+) versus Gram (−) bacterial clearance has not been investigated. In this study, we show that opioid treatment resulted in reduced phagocytosis of Gram (+), when compared to Gram (−) bacteria. We further established that LPS priming of chronic morphine treated macrophages leads to potentiated phagocytosis and killing of both Gram (+) and Gram (−) bacteria in a P-38 MAP kinase dependent signaling pathway. In contrast, LTA priming lead to inhibition of both phagocytosis and bacterial killing. This study demonstrates for the first time the differential effects of TLR4 and TLR2 agonists on morphine induced inhibition of phagocytosis. Our results suggest that the incidence and severity of secondary infections with Gram (+) bacteria would be higher in opioid abusers.

scholarly journals Tumor necrosis factor/cachectin. Induction of hemorrhagic necrosis in normal tissue requires the fifth component of complement (C5).

1988 ◽  
Vol 168 (6) ◽  
pp. 2007-2021 ◽  
Author(s):  
J L Rothstein ◽  
T F Lint ◽  
H Schreiber
Keyword(s):  
Bacterial Infections ◽  
Defense Mechanism ◽  
Normal Skin ◽  
Membrane Attack Complex ◽  
Tissue Response ◽  
Mouse Strains ◽  
Plasma Fraction ◽  
Hemorrhagic Necrosis ◽  
Rapid Spread ◽  
Deficient Mice

TNF induces hemorrhagic necrosis (HN) when injected into skin exposed to bacterial agents but not when injected into normal skin. In this paper, we present several lines of evidence suggesting that TNF requires the fifth component of complement (C5) to induce HN in skin exposed to bacteria. First, mouse strains that do not have C5 did not develop HN after injection of TNF and bacteria into skin. Second, plasma from C5-sufficient mice could correct the defect in these C5-deficient mice. Third, heating at 56 degrees C for 30 min inactivated the capacity of plasma to reconstitute C5-deficient mice. Fourth, CVF, which is known to inactivate complement, abrogated the capability of C5-sufficient mice to respond. Fifth, depleting plasma of hemolytic activity while generating C5a did not affect the capacity of the activated plasma to reconstitute C5-deficient mice. Finally, only the plasma fraction containing molecules of the size range of C5a reconstituted C5-deficient mice. These findings indicate that C5a and not the membrane attack complex is required for HN. Although we do not know through which mechanism C5a participates in the development of HN, we propose that the described HN response is related to a local defense mechanism in which TNF and C5a lead to the disruption of capillaries in the direct vicinity of bacteria. By this mechanism the rapid spread of bacteria or their products into the circulation is prevented. Such a tissue response is consistent with the known higher susceptibility of C5-deficient mice to bacterial infections and provides a model with which to search for the multiple steps involved in this important local defense mechanism.

scholarly journals Overexpression of the Oral Mucosa-Specific microRNA-31 Promotes Skin Wound Closure

2019 ◽  
Vol 20 (15) ◽  
pp. 3679 ◽  
Author(s):  
Lin Chen ◽  
Alyne Simões ◽  
Zujian Chen ◽  
Yan Zhao ◽  
Xinming Wu ◽  
...  
Keyword(s):  
Wound Healing ◽  
Oral Mucosa ◽  
Wound Closure ◽  
Expression Patterns ◽  
Skin Wound ◽  
Skin Wound Healing ◽  
Specific Expression ◽  
Keratinocyte Proliferation

Wounds within the oral mucosa are known to heal more rapidly than skin wounds. Recent studies suggest that differences in the microRNAome profiles may underlie the exceptional healing that occurs in oral mucosa. Here, we test whether skin wound-healing can be accelerating by increasing the levels of oral mucosa-specific microRNAs. A panel of 57 differentially expressed high expresser microRNAs were identified based on our previously published miR-seq dataset of paired skin and oral mucosal wound-healing [Sci. Rep. (2019) 9:7160]. These microRNAs were further grouped into 5 clusters based on their expression patterns, and their differential expression was confirmed by TaqMan-based quantification of LCM-captured epithelial cells from the wound edges. Of these 5 clusters, Cluster IV (consisting of 8 microRNAs, including miR-31) is most intriguing due to its tissue-specific expression pattern and temporal changes during wound-healing. The in vitro functional assays show that ectopic transfection of miR-31 consistently enhanced keratinocyte proliferation and migration. In vivo, miR-31 mimic treatment led to a statistically significant acceleration of wound closure. Our results demonstrate that wound-healing can be enhanced in skin through the overexpression of microRNAs that are highly expressed in the privileged healing response of the oral mucosa.

scholarly journals AMPK activates Parkin independent autophagy and improves post sepsis immune defense against secondary bacterial lung infections

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nathaniel B. Bone ◽  
Eugene J. Becker ◽  
Maroof Husain ◽  
Shaoning Jiang ◽  
Anna A. Zmijewska ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Inflammatory Responses ◽  
Abdominal Sepsis ◽  
Immune Defense ◽  
Bacterial Killing ◽  
Lung Infections ◽  
Sepsis Survivors ◽  
The Impact

AbstractMetabolic and bioenergetic plasticity of immune cells is essential for optimal responses to bacterial infections. AMPK and Parkin ubiquitin ligase are known to regulate mitochondrial quality control mitophagy that prevents unwanted inflammatory responses. However, it is not known if this evolutionarily conserved mechanism has been coopted by the host immune defense to eradicate bacterial pathogens and influence post-sepsis immunosuppression. Parkin, AMPK levels, and the effects of AMPK activators were investigated in human leukocytes from sepsis survivors as well as wild type and Park2−/− murine macrophages. In vivo, the impact of AMPK and Parkin was determined in mice subjected to polymicrobial intra-abdominal sepsis and secondary lung bacterial infections. Mice were treated with metformin during established immunosuppression. We showed that bacteria and mitochondria share mechanisms of autophagic killing/clearance triggered by sentinel events that involve depolarization of mitochondria and recruitment of Parkin in macrophages. Parkin-deficient mice/macrophages fail to form phagolysosomes and kill bacteria. This impairment of host defense is seen in the context of sepsis-induced immunosuppression with decreased levels of Parkin. AMPK activators, including metformin, stimulate Parkin-independent autophagy and bacterial killing in leukocytes from post-shock patients and in lungs of sepsis-immunosuppressed mice. Our results support a dual role of Parkin and AMPK in the clearance of dysfunctional mitochondria and killing of pathogenic bacteria, and explain the immunosuppressive phenotype associated Parkin and AMPK deficiency. AMPK activation appeared to be a crucial therapeutic target for the macrophage immunosuppressive phenotype and to reduce severity of secondary bacterial lung infections and respiratory failure.

Fabrication of gelatin/sodium alginate-poly (3-hydroxybutyric acid) bilayer electrospun biosheet as wound healing material in nursing care on pediatric fracture surgery

2020 ◽  
pp. 152808372097634
Author(s):  
Daiqi Jiang ◽  
Zaiju Tong ◽  
Lingjun Peng ◽  
Lingzhi Zhang ◽  
Qianzi Ruan ◽  
...  
Keyword(s):  
Wound Healing ◽  
Sodium Alginate ◽  
Wound Closure ◽  
Skin Wound ◽  
Tissue Formation ◽  
Hydroxybutyric Acid ◽  
Physiochemical Properties ◽  
Pediatric Fracture ◽  
Fracture Surgery

Novel the bilayered electrospun biosheet with rapid cell mimiciking and proliferative efficacy will be suitable for wound healing application. The optimized concentration of gelatin (G) and sodium alginate (A) biosheet with nanofibrous Poly (3-hydroxybutyric acid) (P) as a bilayered elctrospun matrix through electrospinning. The engineered GAP bilayered biosheet involves tissue formation at extra cellular matrix (ECM) which further characterized its function in vitro and invivo. Here we fabricated GAP which exhibit better physiochemical properties, biological and mechanical properties with superior prosomes it enhance air passable at skin wounds. The Bilayered biosheet matrix possess better biocompatibility, cell adherence, fructuous and cell to cell interactions evaluated using cell lines. Furthermore, GAP bilayered matrix regulates growth factors to attain maximum wound closure efficiency during invivo. Thus, the fabricated GAP electrospun biosheet would be a possible wound dressing for skin wound applications.

scholarly journals Skin stretch suturing with Nice knots in the treatment of small- or medium-sized wounds

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Jianmin Xu ◽  
Rui Chang ◽  
Wei Zhang ◽  
Chengcheng Zhang ◽  
Dezhi Zhu ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Hair Growth ◽  
Wound Closure ◽  
Skin Wound ◽  
Soft Tissue Defects ◽  
Cutaneous Sensation ◽  
The Mean ◽  
Skin Stretch ◽  
Mean Time ◽  
Tissue Defects

Abstract Background To investigate the clinical efficacy and outcomes of skin stretch suturing with self-locking sliding Nice knots in the treatment of small- or medium-sized wounds. Methods From June 2015 to May 2018, 26 patients with small- or medium-sized wounds were included in the present study. Skin stretch suturing with self-locking slide Nice knots was performed to gradually close the soft-tissue defects in these patients. The time of wound closure and healing was recorded. The color and blood supply of the skin, cutaneous sensation, the stretch of skin, and the hair growth situation of the skin wound were observed and recorded. Results There were 17 males and 9 females with an average age of 30.65 years (range, 15–48 years). The areas of the soft-tissue defects were between 3.2 × 7.1 cm and 8.0 × 15.2 cm. All patients underwent stretch suturing with self-locking slide Nice knots to close the soft-tissue defects. All wounds were successfully closed and healed. The mean time of wound closure was 10.69 days (range, 5–20 days), and the mean time of wound healing was 16.85 days (range, 10–24 days). The cutaneous sensation of skin wound recovered normally, and the color of the skin wounds was the same as that of normal skin at the last follow-up. The hair growth situation of the skin wounds also returned to normal. Conclusions This study revealed that Nice knots yielded an accepted clinical result as a new method to close small- or medium-sized wounds that was simple and less minimally invasive, resulted in progressive tension, did not return to previous results, and partially replace flaps or free skin grafts.

scholarly journals Total arterial myocardial revascularization using bilateral internal mammary arteries and the role of postoperative sternal stabilization to reduce wound infections in a large cohort study

2019 ◽  
Vol 29 (2) ◽  
pp. 224-229 ◽  
Author(s):  
Marc Albert ◽  
Ragi Nagib ◽  
Adrian Ursulescu ◽  
Ulrich F W Franke
Keyword(s):  
Retrospective Study ◽  
Wound Infection ◽  
Internal Mammary Artery ◽  
Wound Closure ◽  
Myocardial Revascularization ◽  
Wound Complications ◽  
Wound Infections ◽  
Term Survival ◽  
Mammary Arteries ◽  
Internal Mammary

Abstract OBJECTIVES Total arterial myocardial revascularization using bilateral internal mammary arteries shows improved results for mortality, long-term survival and superior graft patency. It has become the standard technique according to recent guidelines. However, these patients may have an increased risk of developing sternal wound infections, especially obese patients or those with diabetes. One reason for the wound complications may be early sternum instability. This situation could be avoided by using a thorax support vest (e.g. Posthorax® vest). This retrospective study compared the wound complications after bilateral internal mammary artery grafting including the use of a Posthorax vest. METHODS Between April 2015 and May 2017, 1613 patients received total arterial myocardial revascularization using bilateral internal mammary artery via a median sternotomy. The Posthorax support vest was used from the second postoperative day. We compared those patients with 1667 patients operated on via the same access in the preceding 26 months. The end points were the incidence of wound infections, when the wound infection occurred and how many wound revisions were needed until wound closure. RESULTS The demographic data of both groups were similar. A significant advantage for the use of a thorax support vest could be seen regarding the incidence of wound infections (P = 0.036) and the length of hospital stay when a wound complication did occur (P = 0.018). CONCLUSIONS As seen in this retrospective study, the early perioperative use of a thorax stabilization vest, such as the Posthorax vest, can reduce the incidence of sternal wound complications significantly. Furthermore, when a wound infection occurred, and the patient returned to the hospital for wound revision, patients who were given the Posthorax vest postoperatively had a significantly shorter length of stay until wound closure.

scholarly journals Human Mucosal Mast Cells Capture HIV-1 and Mediate Viraltrans-Infection of CD4+T Cells

2015 ◽  
Vol 90 (6) ◽  
pp. 2928-2937 ◽  
Author(s):  
Ai-Ping Jiang ◽  
Jin-Feng Jiang ◽  
Ji-Fu Wei ◽  
Ming-Gao Guo ◽  
Yan Qin ◽  
...  
Keyword(s):  
T Cells ◽  
Mast Cells ◽  
Cell Surface ◽  
Bacterial Infections ◽  
Mucosal Mast Cells ◽  
Mucosal Tissues ◽  
Viral Particles ◽  
Molecular Patterns ◽  
Hiv 1

ABSTRACTThe gastrointestinal mucosa is the primary site where human immunodeficiency virus type 1 (HIV-1) invades, amplifies, and becomes persistently established, and cell-to-cell transmission of HIV-1 plays a pivotal role in mucosal viral dissemination. Mast cells are widely distributed in the gastrointestinal tract and are early targets for invasive pathogens, and they have been shown to have increased density in the genital mucosa in HIV-infected women. Intestinal mast cells express numerous pathogen-associated molecular patterns (PAMPs) and have been shown to combat various viral, parasitic, and bacterial infections. However, the role of mast cells in HIV-1 infection is poorly defined. In this study, we investigated their potential contributions to HIV-1 transmission. Mast cells isolated from gut mucosal tissues were found to express a variety of HIV-1 attachment factors (HAFs), such as DC-SIGN, heparan sulfate proteoglycan (HSPG), and α4β7 integrin, which mediate capture of HIV-1 on the cell surface. Intriguingly, following coculture with CD4+T cells, mast cell surface-bound viruses were efficiently transferred to target T cells. Prior blocking with anti-HAF antibody or mannan before coculture impaired viraltrans-infection. Cell-cell conjunctions formed between mast cells and T cells, to which viral particles were recruited, and these were required for efficient cell-to-cell HIV-1 transmission. Our results reveal a potential function of gut mucosal mast cells in HIV-1 dissemination in tissues. Strategies aimed at preventing viral capture and transfer mediated by mast cells could be beneficial in combating primary HIV-1 infection.IMPORTANCEIn this study, we demonstrate the role of human mast cells isolated from mucosal tissues in mediating HIV-1trans-infection of CD4+T cells. This finding facilitates our understanding of HIV-1 mucosal infection and will benefit the development of strategies to combat primary HIV-1 dissemination.

scholarly journals Mast Cell-Specific Expression of Human Siglec-8 in Conditional Knock-in Mice

2018 ◽  
Vol 20 (1) ◽  
pp. 19 ◽  
Author(s):  
Yadong Wei ◽  
Krishan Chhiba ◽  
Fengrui Zhang ◽  
Xujun Ye ◽  
Lihui Wang ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Mast Cell ◽  
Mast Cells ◽  
Es Cells ◽  
Embryonic Stem ◽  
Surface Protein ◽  
Cell Types ◽  
Mouse Strains ◽  
Specific Expression

Sialic acid-binding Ig-like lectin 8 (Siglec-8) is expressed on the surface of human eosinophils, mast cells, and basophils—cells that participate in allergic and other diseases. Ligation of Siglec-8 by specific glycan ligands or antibodies triggers eosinophil death and inhibits mast cell degranulation; consequences that could be leveraged as treatment. However, Siglec-8 is not expressed in murine and most other species, thus limiting preclinical studies in vivo. Based on a ROSA26 knock-in vector, a construct was generated that contains the CAG promoter, a LoxP-floxed-Neo-STOP fragment, and full-length Siglec-8 cDNA. Through homologous recombination, this Siglec-8 construct was targeted into the mouse genome of C57BL/6 embryonic stem (ES) cells, and chimeric mice carrying the ROSA26-Siglec-8 gene were generated. After cross-breeding to mast cell-selective Cre-recombinase transgenic lines (CPA3-Cre, and Mcpt5-Cre), the expression of Siglec-8 in different cell types was determined by RT-PCR and flow cytometry. Peritoneal mast cells (dual FcεRI+ and c-Kit+) showed the strongest levels of surface Siglec-8 expression by multicolor flow cytometry compared to expression levels on tissue-derived mast cells. Siglec-8 was seen on a small percentage of peritoneal basophils, but not other leukocytes from CPA3-Siglec-8 mice. Siglec-8 mRNA and surface protein were also detected on bone marrow-derived mast cells. Transgenic expression of Siglec-8 in mice did not affect endogenous numbers of mast cells when quantified from multiple tissues. Thus, we generated two novel mouse strains, in which human Siglec-8 is selectively expressed on mast cells. These mice may enable the study of Siglec-8 biology in mast cells and its therapeutic targeting in vivo.

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