Upregulation of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in renal tissue in severe dengue in humans: Effects on endothelial activation/dysfunction

Abstract

Introduction: Dengue is an important mosquito-borne disease in tropical and subtropical regions. Adhesion molecules have not been systematically characterized in the renal tissue of patients with severe dengue (SD). The objective of this study was to detect viral antigens in samples from patients that evolved with SD, correlating with the expression of ICAM-1, VCAM-1, VE-cadherin, and E-selectin to contribute to a better understanding of the pathophysiology of SD. Methods: Kidney specimens from patients with SD were selected according to clinical and laboratorial data and submitted to histological and immunohistochemistry analysis. A semiquantitative evaluation was performed considering positive immunostaining in 20 glomeruli. Results: Viral antigens were mainly detected in distal tubules. The intense immunostaining of VCAM-1 and ICAM-1 was observed. The expression of E-selectin was discrete, and VE-cadherin expression varied from mild to moderate. VCAM-1 was slightly intense in the glomerular capsule; the expression of ICAM-1 was diffuse. E-selectin was diffuse, and VE-cadherin varied from mild to moderate. The most frequent histological findings were glomerular congestion, mild glomerulitis, acute renal injury, and glomerular atrophy. Conclusions: The results appear to demonstrate an imbalance between vascular endothelial permeability regulating events in renal lesions in SD. The increase in the expression of ICAM-1 and VCAM-1 is an in-situ indicator of higher permeability with a consequent influx of cells favoring the inflammation of the endothelium. These molecules are important in the pathophysiology of the disease and provide the possibility of developing new markers for the evaluation, clinical follow-up, and therapeutic response of patients with SD.

Identification of COVID-19 and Dengue Host Factor Interaction Networks Based on Integrative Bioinformatics Analyses

“…In dengue, increased expression of ICAM-1 can result in the consequent influx of cells promoting inflammation of the endothelium. Relevant studies are in favor of the development of new markers for the evaluation, therapeutic response, and clinical follow-up of patients with severe dengue ( 69 ). Thus, ICAM-1 might be important for co-infection.…”

Cytokine Signature of Dengue Patients at Different Severity of the Disease

“…During disease progression, infected cells produce inflammatory cytokines such as TNF-α, IL-6, and IL-10. As a result of this stimulation, endothelial cells increase the expression of adhesion molecules such as CD62E (E-Selectin), CD106 (VCAM-1) and CD62P (P-Selectin) which leads to local inflammation, endothelial damage and plasma leakage [25][26][27]. Hence, our results demonstrated that adhesion molecules like CD54, CD106, CD62E, CD62L, CD62P and CD154, based upon the days of fever, all exhibited this fluctuation in their expression starting from day 0 when compared to the healthy control mean (baseline) but become more normal (baseline) in the recovery phase after day 8 Figure 3.…”

Viral Endothelial Dysfunction: A Unifying Mechanism for COVID-19

“…20,22,25,26 The dengue virus is thought to be associated with endothelial injury, which in turn leads to widespread vascular leakage evident at day 3 to 6 after the onset of illness. 27,28 This timing is similar to the onset of severe illness after SARS-CoV-2 infection. The dengue virus targets dendritic cells and monocytes/macrophages, which after becoming infected induce release of chemokines and cytokines that activate endothelial cells, increase vascular permeability, and impair vascular function and perfusion (Figure 2).…”

“…This in turn has been reported to lead to reduced multiorgan failure and morbidity and mortality. [27][28][29][30] Chronic HIV infection also is widely known to be associated with endothelial dysfunction, but there is evidence that even in the acute setting HIV can result in endothelial injury and dysfunction. 22,26,31 In a ARTICLE HIGHLIGHTS d Severe acute respiratory syndrome coronavirus 2 is a highly transmissible virus that has led to a global pandemic.…”