Evaluation of Endocan as a Treatment for Acute Inflammatory Respiratory Failure.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a life-threatening condition resulting from acute pulmonary inflammation. However, no specific treatment for ARDS has yet been developed. Previous findings suggest that lung injuries related to ARDS could be regulated by endocan (Esm-1). The aim of this study was to evaluate the potential efficiency of endocan in the treatment of ARDS. METHODS: We first compared the features of acute pulmonary inflammation and the severity of hypoxemia in a tracheal LPS-induced acute lung injury (ALI) model performed in knockout (Esm1-/-) and wild type (WT) littermate C57Bl/6 mice. Next, we assessed the effects of a continuous infusion of glycosylated murine endocan in our ALI model in Esm1-/- mice. RESULTS: In our ALI model, we report higher alveolar leukocytes (p < 0.001), neutrophils (p < 0.001), and MPO (p < 0.001), and lower blood oxygenation (p < 0.001) in Esm1-/- mice compared to WT mice. Continuous delivery of glycosylated murine endocan after LPS-induced ALI resulted in decreased alveolar leukocytes (p = 0.012) and neutrophils (p = 0.012), higher blood oxygenation levels (p < 0.001), and reduced histological lung injury (p = 0.04), compared to mice treated with PBS. CONCLUSIONS: Endocan appears to be an effective treatment in an ARDS-like model in C57Bl/6 mice.

Saving lives by ventilating two patients with specific pressure-controlled ventilation from a single ICU-ventilator during the COVID-19 pandemic.

In late December 2019, SARS-CoV-2 was discovered, which is responsible for a new human disease called COVID-19. Among all laboratory-confirmed COVID-19 cases, 14% were hospitalized, with 2% admitted to intensive care units (ICU) with acute respiratory distress syndrome (ARDS) requiring mechanical ventilation [1]. SARS-CoV-2 has spread quickly across the world, with more than one hundred million confirmed cases and more than 2,500,000 dead. In March 2020, the Hospital of Valenciennes had to admit hundreds of COVID-19 patients, and its capacity was almost exceeded [2]. More recently, in France, thousands of critically ill patients had to be admitted to ICUs. In Europe, the next wave of COVID-19 pandemic could be more severe than the first one, and we already know that, in the case of increasing numbers of critically ill, some of them will die as a result of the unavailability of mechanical ventilators [3]. This shortage may be lessened if one ventilator could service more than one patient. The main worry is that this concept could be not useful and systematically deleterious for the patient. Some concepts have already been proposed to ventilate differently two circuits with a single ventilator, with several limitations like the lack of individualization of ventilation of each circuit [4-6]. More recently, in the face of the COVID-19 pandemic, Clarke et al. [7] described a new concept able to deliver specific ventilation for two different lung tests with a single ventilator. Again, Levin et al. [8] have recently shown that a similar concept of differential ventilation using a single ventilator with flow control valves is feasible in humans.

Cleaved endocan acts as a biologic competitor of endocan in the control of ICAM-1-dependent leukocyte diapedesis.

Dysregulated leukocyte diapedesis is a major contributor to acute severe inflammatory states like sepsis and acute respiratory distress syndrome, which are common conditions in critically ill subjects. Endocan is a circulating proteoglycan that binds to the leukocyte integrin LFA-1 and blocks its interaction with its endothelial ligand ICAM-1, subsequently leading to the inhibition of leukocyte recruitment. Recent data have highlighted the hypothetic role of p14, endocan's major catabolite found in the bloodstream of septic patients, as a potential antagonist of endocan, thus participating in the regulation of acute inflammation. We hereby characterize the role of p14 as a biologic competitor of endocan, through assessment of its molecular interactions with LFA-1, endocan, and ICAM-1, as well as its effects on human leukocyte trafficking. Using immunodetection assay, we report that p14 can bind to LFA-1, thus inhibiting the interaction between LFA-1 and endocan, which in turn leads to the restoration of the ICAM-1/LFA-1 interaction. In primary human T cells trafficking assays, we underline the absence of effect of p14 on ICAM-1-dependent adhesion and migration, as well as on transendothelial migration. However, in those models, p14 reverses the antimigratory effect of endocan. To conclude, our study supports the hypothesis of an antagonistic role of p14 versus endocan in its effect on the LFA-1/ICAM-1-dependent human leukocyte recruitment.