Leukocyte apoptosis in whole blood involves platelet‐dependent coaggregation

Hartz, S.; Menart, Barbara; Tschöepe, Diethelm

doi:10.1002/cyto.a.10026

Cited by 19 publications

(19 citation statements)

References 27 publications

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“…Apoptosis plays a role in the tissue damage caused by chronic complications in DM2 (22)(23)(24)(25)(26). Apoptosis during acute complications of a chronic condition such as diabetic foot may be explained by at least 5 mechanisms: high glucose concentration (27)(28)(29)(30)(31), ketoacidosis, systemic inflammatory response (32), infection and hypoxia.…”

Section: Discussionmentioning

confidence: 99%

TUNEL-positive cells in the surgical border of an amputation due to infected diabetic foot

et al. 2011

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Abstract. Diabetic infected foot is the outcome of progressive vascular and neurological damage caused by persistent chronic hyperglycemia. Due to acute hypoxia and infection, the tissues develop extensive necrosis and gangrene, which often require amputation. The decision regarding the level of amputation relies mainly on the personal experience of the surgeon who must identify the healthy tissue without necrosis. However, tissue cells under stress may succumb before clear evidence of necrosis is present. In this study, dying cells with DNA damage were identified in the necrotic lesions and surgical borders of amputations. Therefore, the main purpose of this study was to identify apoptosis in the surgical borders of amputations required to treat infected diabetic foot. Apoptosis was identified by terminal deoxynucleotidyl transferase-mediated bio-dUTP nick-end labeling (TUNEL) in the superficial and deep tissues of wounds, and in the surgical borders of 10 consecutive adult patients with diabetes mellitus type 2 (DM2) who underwent amputation due to infected diabetic foot. The severity of the disease was classified by the Acute Physiological and Chronic Health Evaluation II (APACHE II) score on admission, and laboratory data were collected and bacteriological cultures were obtained from the lesions. The ankle/arm blood pressure index was measured, the blood flow in the affected limb was evaluated by high-resolution ultrasonography and color Doppler and pulse oximetry were performed during surgery. A total of 5 males and 5 females, aged 45-84 years (58.8±14.1), were included. The APACHE II score was 2-18 points (8±5.7). A total of 9 patients developed sepsis and 2 succumbed. A total of 5 patients required above-ankle amputation, and 5 required toe disarticulation. The ankle/ arm blood pressure index ranged from 0.23-0.85 (0.51±0.23). Apoptotic cells were found in ulcers and abscesses, and in areas without necrosis. In the surgical borders of the amputations, apoptotic cells were found in skeletal muscle, blood vessels and periphe ral nerves, particularly Schwann cells. Morphometric analysis revealed that the extent of apoptosis was 2-3 logarithms higher in the surgical borders of the infected diabetic foot compared to the venous ulcers, which were used as the reference. In conclusion, apoptosis was identified in regenerating tissues within diabetic foot wounds and in the surgical borders of amputations, where the surgeon considered the tissues to be undamaged. This information suggests that apoptosis may be present before visible signs of necrosis appear in the diabetic foot and may be caused by hypoxia, acidosis or proinflammatory cytokines. The extent of apoptosis in tissues proximal to necrotic areas may anticipate the development of diabetic foot and help the surgeon to make decisions regarding the need and extent of amputation.

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Section: Discussionmentioning

confidence: 99%

TUNEL-positive cells in the surgical border of an amputation due to infected diabetic foot

et al. 2011

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“…In activated samples, platelet microparticles [103, 104, 115], platelet aggregates [116], and leukocyte-platelet aggregates [117, 118] are formed (Figure 1). In particular, platelet activation in whole blood induces the formation of platelet conjugates with granulocytes or monocytes [119] and leukocyte aggregates with platelets are more prone to apoptosis after in vitro activation (Figure 1) [117].…”

Section: Measurement Of Reactive Species In Leukocytes and Platelementioning

confidence: 99%

Measurement and Clinical Significance of Biomarkers of Oxidative Stress in Humans

Marrocco

Altieri

Peluso

2017

Oxidative Medicine and Cellular Longevity

647

500

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Oxidative stress is the result of the imbalance between reactive oxygen species (ROS) formation and enzymatic and nonenzymatic antioxidants. Biomarkers of oxidative stress are relevant in the evaluation of the disease status and of the health-enhancing effects of antioxidants. We aim to discuss the major methodological bias of methods used for the evaluation of oxidative stress in humans. There is a lack of consensus concerning the validation, standardization, and reproducibility of methods for the measurement of the following: (1) ROS in leukocytes and platelets by flow cytometry, (2) markers based on ROS-induced modifications of lipids, DNA, and proteins, (3) enzymatic players of redox status, and (4) total antioxidant capacity of human body fluids. It has been suggested that the bias of each method could be overcome by using indexes of oxidative stress that include more than one marker. However, the choice of the markers considered in the global index should be dictated by the aim of the study and its design, as well as by the clinical relevance in the selected subjects. In conclusion, the clinical significance of biomarkers of oxidative stress in humans must come from a critical analysis of the markers that should give an overall index of redox status in particular conditions.

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“…It is characterised by typical features, including cell shrinkage and rounding, condensation of nuclear chromatin and its clumping against the nuclear envelope, and membrane blebbing 7. Apoptotic leucocytes trigger adhesion, platelet activation, and leucocyte–platelet aggregation, thus constituting a prothrombotic state which endangers the microcirculation of septic patients 8. As the neutrophils’ apoptosis influences the host response outcome, its timely detection provides additional information regarding the course of the disease 8 – 13…”

Section: Infection Related Alterations Of Blood Cell Morphologymentioning

confidence: 99%

The added value of peripheral blood cell morphology in the diagnosis and management of infectious diseases—part 1: basic concepts

Prokocimer

Potasman

2008

Postgraduate Medical Journal

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As automated blood cell analysers and sophisticated diagnostic technologies become widespread, requests for peripheral blood smear (PBS) examination--for the diagnosis of infectious diseases--diminish. Yet, PBS examination can provide rapid and invaluable information on infection--host susceptibility, aetiology, severity, and systemic impact. Besides direct visualisation of certain microorganisms (for example, Plasmodium, Ehrlichia), PBS examination may detect characteristic footprints left by various infections on the morphology of blood cells, thus yielding the cytologic clues of the disease (for example, Döhle bodies, haemophagocytosis). Additionally, PBS examination may disclose certain infection predisposing conditions (for example, May-Hegglin anomaly, hyposplenism), and several infection related haematological and systemic complications. Combined with a careful medical history and physical examination data, all this information may yield a speedy diagnosis, a rationalised diagnostic work-up, and timely initiation of treatment. The intention of the following review is to highlight the value of PBS, and recommend that PBS examination should be fostered in the diagnostic work-up of infectious diseases.

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Leukocyte apoptosis in whole blood involves platelet‐dependent coaggregation

Cited by 19 publications

References 27 publications

TUNEL-positive cells in the surgical border of an amputation due to infected diabetic foot

TUNEL-positive cells in the surgical border of an amputation due to infected diabetic foot

Measurement and Clinical Significance of Biomarkers of Oxidative Stress in Humans

The added value of peripheral blood cell morphology in the diagnosis and management of infectious diseases—part 1: basic concepts

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