Heparanase is an endo-b-glucuronidase that cleaves heparan @entity597 side chains from their proteoglycans. Thereby, heparanase liberates highly potent circulating heparan @entity597 -fragments (HS-fragments) and triggers the fatal and excessive inflammatory response in @entity295 . As a potential anti-inflammatory agent for @entity295 therapy, peptide 19-2.5 belongs to the class of synthetic anti-lipopolysaccharide peptides; however, its activity is not restricted to Gram-negative @entity2348 . We hypothesized that peptide 19-2.5 interacts with heparanase and/or HS, thereby reducing the levels of circulating HS-fragments in @entity19 and @entity1 @entity295 . Our data indicate that the treatment of septic @entity19 with peptide 19-2.5 compared to untreated control animals lowers levels of plasma heparanase and circulating HS-fragments and reduces heparanase activity. Additionally, mRNA levels of heparanase in heart, liver, lung, kidney and spleen are downregulated in septic @entity19 treated with peptide 19-2.5 compared to untreated control animals. In @entity1 , plasma heparanase level and activity are elevated in @entity326 . The ex vivo addition of peptide 19-2.5 to plasma of @entity326 @entity1 decreases heparanase activity but not heparanase level. Isothermal titration calorimetry revealed a strong exothermic reaction between peptide 19-2.5 and heparanase and HS-fragments. However, a saturation character has been identified only in the peptide 19-2.5 and HS interaction. In conclusion, the findings of our current study indicate that peptide 19-2.5 interacts with heparanase, which is elevated in @entity19 and @entity1 @entity295 and consecutively attenuates the generation of circulating HS-fragments in systemic @entity32 . Thus, peptide 19-2.5 seems to be a potential anti-inflammatory agent in @entity295 .

The Synthetic Antimicrobial Peptide 19-2.5 Interacts with Heparanase and Heparan XXXX in @entity19 and @entity1 Sepsis.

@entity1 :: ('9606', 'Species') :: ['humans', 'human', 'patients'] @entity32 :: ('MESH:D007249', 'Disease') :: ['inflammation'] @entity295 :: ('MESH:D018805', 'Disease') :: ['sepsis'] @entity326 :: ('MESH:D012772', 'Disease') :: ['septic shock'] @entity19 :: ('10090', 'Species') :: ['mice', 'murine'] @entity2348 :: ('MESH:D001424', 'Disease') :: ['bacterial infection'] @entity597 :: ('CHEBI:16189', 'Chemical') :: ['sulfate']
@entity597 :: (CHEBI:16189,Chemical) :: ['Sulfate']
