Nitric oxide and wound repair

Schwentker, Ann; Billiar, Timothy R.

doi:10.1016/s0039-6109(02)00207-4

Cited by 85 publications

(81 citation statements)

References 59 publications

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“…We also examined the impact of a proinflammatory environment, again because such a reaction is known to occur during and to be crucial for the healing process. To demonstrate the expression of the TLRs on the protein level and therefore the functionality of the receptors, we examined the relatively early event of IL-8 secretion, a well-known endothelial function serving leukocyte recruitment, and the comparatively late event of iNOS expression, a hallmark of inflammation and an important reaction in the wound-healing process (12,20,25).…”

Section: Discussionmentioning

confidence: 99%

Human Skin Endothelial Cells Can Express All 10TLRGenes and Respond to Respective Ligands

Fitzner

Clauberg

Eßmann

et al. 2008

Clin Vaccine Immunol

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Breakdown of the skin barrier requires the recognition of and rapid responses to invading pathogens. Since wounding usually also affects endothelial intactness, the expression of receptors of the Toll-like family involved in pathogen recognition in human skin vessel endothelia was examined. We found that human skin-derived microvascular endothelial cells can express all 10 Toll-like receptors (TLRs) currently known and will respond to respective ligands. Using immortalized skin-derived (HMEC-1) and primary dermal endothelial cells (HDMEC), we screened for TLR expression by real-time PCR. Endothelial cells express 7 (for HDMEC) and 8 (for HMEC-1) of the 10 known human TLRs under resting conditions but can express all 10 receptors in proinflammatory conditions. To provide evidence of TLR functionality, endothelial cells were challenged with TLR ligands, and after the TLR downstream signaling, MyD88 recruitment as well as early (interleukin-8 [IL-8] release) and late immune markers (inducible nitric oxide synthase mRNA expression) were monitored. Surprisingly, the responses observed were not uniform but were highly specific depending on the respective TLR ligand. For instance, lipopolysaccharides highly increased IL-8 release, but CpG DNA induced significant suppression. Additionally, TLR-specific responses were found to differ between resting and activated endothelial cells. These results show that human skin-derived endothelial cells can function as an important part of the innate immune response, can actively sense pathogen-associated molecular patterns, and can mount an increased or reduced inflammatory signal upon exposure to any of the currently known TLR ligands. Moreover, we also show here that proinflammatory conditions may affect TLR expression in a specific and nonuniform pattern.

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Section: Discussionmentioning

confidence: 99%

Human Skin Endothelial Cells Can Express All 10TLRGenes and Respond to Respective Ligands

Fitzner

Clauberg

Eßmann

et al. 2008

Clin Vaccine Immunol

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“…16,24,25,29 NOx determinations have been proven to be highly sensitive in documenting declines in NO production associated with impaired wound healing and enhanced NO delivery associated with improved chronic wound recovery. In the present study, HBOT was the intervention, and a progressive increase in wound fluid NOx occurred when HBOT was started; the increase was statistically significant at 1 and 4 weeks after HBOT.…”

Section: Discussionmentioning

confidence: 99%

“…16,24,25,29 NOx determinations have been proven to be highly sensitive in documenting declines in NO production associated with impaired wound healing and enhanced NO delivery associated with improved chronic wound recovery. Impaired wound healing caused by diabetes, 24 proteincalorie malnutrition, 30 cutaneous irradiation, 31 steroid therapy, 32 and metabolic inhibition of NO synthesis 33 was associated with reductions in wound fluid NOx levels.…”

Section: Discussionmentioning

confidence: 99%

“…14,15 Ongoing experimental and clinical wound healing studies have established NO as a critical mediator of normal tissue repair. 16 Angiogenesis, granulation tissue formation, epidermal migration, collagen deposition, and microvascular homeostasis are significant processes critical to normal wound repair that are regulated by NO production and bioactivity. [17][18][19][20] Functional recovery of cutaneous vascular beds after ischemia-reperfusion injury 21 and increased local random tissue flap survival 22 have also been linked to increased vascular endothelial NOS activity in experimental models.…”

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confidence: 99%

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Hyperbaric Oxygen Therapy Mediates Increased Nitric Oxide Production Associated With Wound Healing

Boykin

Baylis

2007

Advances in Skin &Amp; Wound Care

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Objective-The objective of this preliminary study was to document general somatic and wound nitric oxide (NO) levels during and after hyperbaric oxygen therapy (HBOT).Design-The study evaluated 6 chronic wound patients that responded favorably to HBOT treatment (20 treatments; 2.0 atmosphere absolute [ATA] × 90 minutes). Successful HBOT was associated with increased wound granulation tissue formation and significantly improved wound closure. Wound fluid and fasting plasma samples were obtained for measurement of nitrate and nitrite (NOx), the stable oxidation products of NO; plasma L-arginine (L-Arg); and asymmetric dimethylarginine (ADMA). NOx measurements were obtained before treatment (baseline), after 10 and 20 treatments, and at 1 and 4 weeks after therapy.Results-Wound fluid NOx levels tended to increase during treatments, were significantly elevated at 1 and 4 weeks after therapy, and correlated with reductions in wound area. Plasma L-Arg and ADMA were unchanged during and after HBOT.Conclusion-This preliminary study documents a significant increase in local wound NO levels (by NOx measurements) after successful HBOT and suggests that this mechanism may be an important factor in promoting enhanced wound healing and wound closure associated with this therapy.Hyperbaric oxygen therapy (HBOT) accelerates the healing of chronic wounds and is now primarily used as an adjunctive therapy in managing selected problem wound healing. [1][2][3][4] Hyperoxia during HBOT is an important mediating factor for wound collagen deposition and cross-linking, 5 neutrophil-dependent microbial killing, 6 and neovascularization. 7 Other HBOT-mediated processes in wound healing include the inhibition of integrin-mediated intravascular leukocyte adhesions and platelet aggregation, 8 enhancement of cutaneous microvascular homeostasis after ischemia-reperfusion syndrome, 9 increased oxygen capacitance and survival of ischemic flaps, 10 and upregulation of platelet-derived growth factor (PDGF) receptor mRNA. 11Experimental normobaric oxygen activates gene expression in human dermal fibroblasts, supporting the concept of oxygen as a possible signal transducer. 12 An additional signaling system modulated by oxygen availability is provided by the naturally occurring oxygen-free radicals (oxidants), or reactive oxygen species (ROS), found in the wound environment. ROS have been observed to increase cellular vascular endothelial growth factor (VEGF) expression and signal transduction that is considered to promote an overall enhancement of the wound healing process. 13 Further, accelerated wound healing during HBOT may be mediated by the combined effects of hyperoxia and the increased local (wound) production of nitric oxide (NO), an important cellular signal for tissue repair. 14,15 Ongoing experimental and clinical wound healing studies have established NO as a critical mediator of normal tissue repair. 16 Angiogenesis, granulation tissue formation, epidermal migration, collagen deposition, and microvascular homeostasis are signi...

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“…75,76 The spin traps could be placed within the gas-permeable devices that are inserted in the wounds, thereby avoiding potential problems from systemic administration of the spin traps. For example, there are concerns that an oversupply of oxygen could have a negative impact on wound healing, either through direct damage or by affecting cell signaling that is needed for effective repair.…”

Section: Monitoring Oxygen In Healing Woundsmentioning

confidence: 99%

Clinical applications of EPR: overview and perspectives

et al. 2004

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The development and use of in vivo techniques for strictly experimental applications in animals has been very successful, and these results now have made possible some very attractive potential clinical applications. The area with the most obvious immediate, effective and widespread clinical use is oximetry, where EPR almost uniquely can make repeated and accurate measurements of pO 2 in tissues. Such measurements can provide clinicians with information that can impact directly on diagnosis and therapy, especially for oncology, peripheral vascular disease and wound healing. The other area of immediate and timely importance is the unique ability of in vivo EPR to measure clinically significant exposures to ionizing radiation 'after-the-fact', such as may occur due to accidents, terrorism or nuclear war. There are a number of other capabilities of in vivo EPR that also potentially could become extensively used in human subjects. In pharmacology the unique capabilities of in vivo EPR to detect and characterize free radicals could be applied to measure free radical intermediates from drugs and oxidative process. A closely related area of potential widespread applications is the use of EPR to measure nitric oxide. These often unique capabilities, combined with the sensitivity of EPR spectra to the immediate environment (e.g. pH, molecular motion, charge) have already resulted in some very productive applications in animals and these are likely to expand substantially in the near future. They should provide a continually developing base for extending clinical uses of in vivo EPR. The challenges for achieving full implementation include adapting the spectrometer for safe and comfortable measurements in human subjects, achieving sufficient sensitivity for measurements at the sites of the pathophysiological processes that are being measured, and establishing a consensus on the clinical value of the measurements.

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Nitric oxide and wound repair

Cited by 85 publications

References 59 publications

Human Skin Endothelial Cells Can Express All 10TLRGenes and Respond to Respective Ligands

Human Skin Endothelial Cells Can Express All 10TLRGenes and Respond to Respective Ligands

Hyperbaric Oxygen Therapy Mediates Increased Nitric Oxide Production Associated With Wound Healing

Clinical applications of EPR: overview and perspectives

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