Activated protein C (APC) is generated from the cleavage of protein C by thrombin coupled to thrombomodulin and, subsequently, is released as protein C activation peptide (papC). The aim of this study was to evaluate the effect of papC on human dermal microvascular endothelial cells (HMEC-1), activated with 5 ng/ /mL TNF-a. Flow cytometry showed that papC inhibited the expression of VCAM-1 and ICAM-1, after activation with TNF-a. Similarly, RT-PCR analysis revealed that 2 and 4 pM papC inhibited the expression of VCAM-1 and IL-8 mRNA in TNF-a-treated HMEC-1. In addition, the expression of endothelial nitric oxide synthase (eNOS) increased in HMEC-1 treated with papC, compared to those without treatment. Furthermore, Jurkat cell adhesion to HMEC-1 induced by TNF-a was significantly inhibited after the addition of papC, compared to HMEC-1 without papC (p = 0.03). Finally, a control peptide analog to papC showed no effect on the expression of ICAM and VCAM on the surface of HMEC-1. In conclusion, our results suggest that papC exerts antiinflammatory effects on endothelial cells.
SARS-CoV-2 contains certain molecules that are related to the presence of immunothrombosis. Here, we review the pathogen and damage-associated molecular patterns. We also study the imbalance of different molecules participating in immunothrombosis, such as tissue factor, factors of the contact system, histones, and the role of cells, such as endothelial cells, platelets, and neutrophil extracellular traps. Regarding the pathogenetic mechanism, we discuss clinical trials, case-control studies, comparative and translational studies, and observational studies of regulatory or inhibitory molecules, more specifically, extracellular DNA and RNA, histones, sensors for RNA and DNA, as well as heparin and heparinoids. Overall, it appears that a network of cells and molecules identified in this axis is simultaneously but differentially affecting patients at different stages of COVID-19, and this is characterized by endothelial damage, microthrombosis, and inflammation.
It is well known that Phaseolus species contains lectins of various specificities 1-4. Runner bean5 and different varieties of Ph.coccineus described by Ochoa et al6, are not specific to human blood groups. They react indistinctly with erythrocytes of the ABO system. However the lectin of Ph. lunatus (lima bean)7 is specific to the blood group type A, a classic example of that specificity. Sometime ago, we discovered a new lectin in a variety of edible bean of Ph. coccineus in the flora of the state of Oaxaca in Mexico, cultivated exclusively in the small community of Jamiltepec, near the Pacific coast, which presented strong hemagglutinating anti-A1 activity. In this report we describe a chromatographic technique for the isolation and purification of this lectin. The molecule is a tetramer with a molecular weight of 120 kDa. It requires Ca++ or Mg++ for activity, and it is inhibited by N-Acetylgalactosamine (GalNac) at concentration of 2.8 mM., NN' N' Triacetylchitotriose, 4-O(4-O-D-Galactopyranosyl) -D-Galatopyranosyl-D-Glucopyranose, and N' Diacetylchitobiose inhibited at moderate concentration (20mM). Conalbumin and ovoalbumin, also inhibited hemagglutination.
Activated protein C (APC) is generated from the cleavage of protein C by thrombin coupled to thrombomodulin and, subsequently, is released as protein C activation peptide (papC). The aim of this study was to evaluate the effect of papC on human dermal microvascular endothelial cells (HMEC-1), activated with 5 ng//mL TNF-α. Flow cytometry showed that papC inhibited the expression of VCAM-1 and ICAM-1, after activation with TNF-a. Similarly, RT-PCR analysis revealed that 2 and 4 pM papC inhibited the expression of VCAM-1 and IL-8 mRNA in TNF-α-treated HMEC-1. In addition, the expression of endothelial nitric oxide synthase(eNOS) increased in HMEC-1 treated with papC, compared to those without treatment. Furthermore, Jurkat cell adhesion to HMEC-1 induced by TNF-a was significantly inhibited after the addition of papC, compared to HMEC-1 without papC (p = 0.03). Finally, a control peptide analog to papC showed no effect on the expression of ICAM and VCAM on the surface of HMEC-1. In conclusion, our results suggest that papC exerts anti-inflammatory effects on endothelial cells.
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