The Loss of MCP-1 Attenuates Cutaneous Ischemia–Reperfusion Injury in a Mouse Model of Pressure Ulcer

Abstract

The formation of pressure ulcers is dependent on multiple factors including ischemia-reperfusion (IR). This study assessed the mechanism of a previously reported murine model of cutaneous IR injury. Three cycles of IR (days 1-3) by external application of two magnetic plates were performed to induce pressure ulcer formation. Increased infiltration of neutrophils and macrophages, and augmented expression of proinflammatory cytokines and inducible nitric oxide synthase (iNOS), were observed during IR cycles. In this model, monocyte chemoattractant protein-1 (MCP-1) was remarkably increased at day 1 in the skin followed by inflammatory cell infiltration. Therefore, IR cycles were performed in MCP-1-deficient (MCP-1(-/-)) mice to evaluate the role of this chemokine in pressure ulcer development. MCP-1(-/-) mice showed reduced macrophage infiltration and expression of tumor-necrosis factor-alpha (TNF)-alpha and iNOS during IR cycles leading to attenuated apoptosis and skin injury. Importantly, MCP-1 played a role in apoptosis and injury via inducing iNOS during the reperfusion rather than the ischemic period. These findings indicate that MCP-1 may be a critical factor for macrophage recruitment and subsequent skin inflammation and injury during IR cycles. We propose that this is a useful model for investigating the mechanism of pressure ulcer formation using various transgenic mice.

<b>Development and repair of experimental pressure ulcers in the rat abdominal wall induced by repeated compression using magnets</b>

“…Hair follicles had almost disappeared, in agreement findings by Şener et al (2006) and Saito et al (2008). Sebaceous glands were damaged and small in size.…”

“…To produce pressure ulcers, the use of magnets has been reported in the literature (Peirce et al, 2000;Reid et al, 2004;Şener et al, 2006;Saito et al, 2008;Wassermann et al, 2009). However, the pressure in previous studies was either not measured or was not as accurate as in our experiment.…”

“…, 2 0 0 9 ) a n d c a u s e d compression by applying a magnet to the skin. Saito et al (2008) pulled up mouse skin, pinched it using two magnets for 12 h 3 times and observed the repair process of pressure ulcers. In our previous study (Hashimoto et al, 2008), the rat abdominal wall was compressed at 100 mmHg (13.3 kPa) for 4 h using magnets; this demonstrated that magnet compression is an appropriate model for studying the pathogenesis of pressure ulcers.…”

Impedance sensing device enables early detection of pressure ulcers in vivo

“…3), we observed that relieving the pressure initially resulted in increased perfusion (reactive hyperaemia) 4,29 as the blood returned to the affected tissue. When blood returns to the ischaemic tissue, it produces reactive oxygen species and free radicals that can accelerate cell death 30,31 . In our model, 1 h of pressure produced mild reversible tissue damage, and 3 h of pressure produced more severe irreversible damage.…”

Adverse outcomes after major surgery in patients with pressure ulcer: A nationwide population-based retrospective cohort study

“…Third, chronic pressure ulcer features persistent chronic inflammation with leukocyte infiltration and release of proinflammatory cytokines [33,34]. Repetitive pressure and relief also lead to cutaneous ischemia-reperfusion injury, causing infiltration of inflammatory cells, deleterious cellular reactions and tissue damage by reactive free oxygen radicals [35]. Extensive evidence shows that chronic inflammation and infection outside the brain are associated with an increased risk of ischemic stroke via endothelial cell dysfunction, impaired fibrinolysis and activation of platelet aggregability altered by immune-mediated inflammatory cells and cytokines [36][37][38][39].…”