Epithelial Barrier Dysfunction as a Mechanism in the Pathogenesis of Multiple Organ Dysfunction

Fink, Mitchell P.; Cotoia, Antonella; Beer‐Stolz, Donna; Liu, Shiguang; Sappington, Penny L.; Delude, Russell L.

doi:10.1002/9783527626151.ch12

Cited by 2 publications

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“…Data in literature showed that circulating progenitors are present at higher levels in septic patients when compared with healthy volunteers, especially at 72 h after the diagnosis of sepsis [27,29]. Sepsis is associated with systemic microcirculation disruption, hemodynamic imbalance and poor peripheral oxygen uptake although oxygen delivery can be maintained pharmacologically [4]. Hypoxic conditions is known to promote activation of the HIF-1 transcriptional system thus enabling cell adaptation to limited environmental oxygen availability.…”

Section: Discussionmentioning

confidence: 99%

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High mobilization of CD133+/CD34+ cells expressing HIF-1α and SDF-1α in septic abdominal surgical patients

et al. 2020

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Background: The control of endothelial progenitor cells (CD133+/CD34+ EPCs) migrating from bone marrow to peripheral blood is not completely understood. Emerging evidence suggests that stromal cell-derived factor-1α (SDF-1α) mediates egression of EPCs from bone marrow, while the hypoxia inducible factor (HIF) transcriptional system regulates SDF-1α expression. Our study aimed to investigate the time course of circulating CD133+/CD34+ EPCs and its correlation with the expression of HIF-1α protein and SDF-1α in postoperative laparoscopic abdominal septic patients. Methods: Postoperative patients were divided in control (C group) and septic group (S group) operated immediately after the diagnosis of sepsis/septic shock. Blood samples were collected at baseline (0), 1, 3 and 7 postoperative days for CD133+/CD34+ EPCs count expressing or not the HIF-1α and SDF-1α analysis. Results: Thirty-two patients in S group and 39 in C group were analyzed. In C group CD133+/CD34+ EPCs count remained stable throughout the study period, increasing on day 7 (173 [0-421] /μl vs baseline: P = 0.04; vs day 1: P = 0.002). In S group CD133+/CD34+ EPCs count levels were higher on day 3 (vs day 1: P = 0.006 and day 7: P = 0.026). HIF-1α expressing CD133+/CD34+ EPCs count decreased on day 1 as compared with the other days in C group (day 0 vs 1: P = 0.003, days 3 and 7 vs 1: P = 0.008), while it was 321 [0-1418] /μl on day 3 (vs day 1; P = 0.004), and 400 [0-587] /μl on day 7 in S group. SDF-1α levels were higher not only on baseline but also on postoperative day 1 in S vs C group (219 [124-337] pg/ml vs 35 [27-325] pg/ml, respectively; P = 0.01). Conclusion: Our results indicate that sepsis in abdominal laparoscopic patients might constitute an additional trigger of the EPCs mobilization as compared with non-septic surgical patients. A larger mobilization of CD133+/ CD34+ EPCs, preceded by enhanced plasmatic SDF-1α, occurs in septic surgical patients regardless of HIF-1α expression therein. Trial registration: ClinicalTrials.gov no. NCT02589535. Registered 28 October 2015.

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Section: Discussionmentioning

confidence: 99%

“…The abdomen (post-operative infection, perforation, anastomotic leak) is the second most common site of sepsis and septic shock in Intensive Care Unit (ICU) [1][2][3][4][5][6]. Sepsis pathophysiology can be schematically described as an early hyper-inflammatory phase followed by a late hypoinflammatory and immunosuppressive phase [7].…”

Section: Introductionmentioning

confidence: 99%

High mobilization of CD133+/CD34+ cells expressing HIF-1α and SDF-1α in septic abdominal surgical patients

et al. 2020

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Circulating stem cells, HIF-1, and SDF-1 in septic abdominal surgical patients: randomized controlled study protocol

Cotoia

Mirabella

Altamura

et al. 2018

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BackgroundSepsis caused by complicated intra-abdominal infection is associated with high mortality. Loss of endothelial barrier integrity, inflammation, and impaired cellular oxygen have been shown to be primary contributors to sepsis. To date, little is known regarding the pathway for the mobilization of endothelial progenitor cells (EPCs) from the bone marrow in sepsis whereas stromal-cell-derived factor 1a (SDF-1a) and hypoxia inducible factor 1 (HIF-1) seem to have a role in the EPC response to hypoxic microenvironments.The aims of the study are: (a) to determine the time course of the levels of circulating EPCs (CD133/CD34), SDF-1a, and HIF-1 in septic patients undergoing major abdominal surgery (group S), (b) to investigate the relationship between CD133/CD34, HIF-1, and SDF-1a, and (c) to investigate the relationship of these factors with the outcome of group S patients treated with standard conventional therapy alone (CT) or with the addition of extracorporeal hemoperfusion therapy (HCT).Methods/designPatients undergoing major abdominal surgery will be allocated into groups: postoperative non-septic patients in an emergency surgical ward (group C) and postoperative septic patients in an intensive care unit (group S). The latter will be randomized to receive CT alone (S1) or with HCT (S2). Healthy volunteers (group H) will be recruited at University Hospital Foggia.Peripheral blood (PB) samples will be collected preoperatively (T0), at 24 h (T1), 72 h (T2), 7 (T3), and 10 (T4) postoperative days in groups S and C, and at T0 in group H. The CD34/133 cells and HIF-1 counts will be determined by flow cytometer analysis. The concentration of SDF-1a in plasma will be calculated by enzyme-linked immunosorbent assay analysis (ELISA).DiscussionThis prospective randomized clinical trial is designed to investigate circulating stem cells, levels of HIF-1 and SDF-1a, and their interrelationship in septic postoperative abdominal surgical patients treated with CT alone or with HCT. The rationale is that an integrated understanding of the role of hypoxia-related factors and EPCs in PB of septic patients could indicate which molecular processes need to be regulated to recover the innate immunity homeostasis. Understanding the function of EPCs in sepsis may provide innovative diagnostic and therapeutic approaches to improve the prognosis of this syndrome.Trial registrationClinicalTrials.gov: NCT02589535. Registered on 28 October 2015.Electronic supplementary materialThe online version of this article (10.1186/s13063-018-2556-0) contains supplementary material, which is available to authorized users.

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Epithelial Barrier Dysfunction as a Mechanism in the Pathogenesis of Multiple Organ Dysfunction

Cited by 2 publications

References 106 publications

High mobilization of CD133+/CD34+ cells expressing HIF-1α and SDF-1α in septic abdominal surgical patients

High mobilization of CD133+/CD34+ cells expressing HIF-1α and SDF-1α in septic abdominal surgical patients

Circulating stem cells, HIF-1, and SDF-1 in septic abdominal surgical patients: randomized controlled study protocol

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