Use of heparinase to decrease inflammatory responses

Abstract

Heparinase enzymes can be used as a medical treatment to reduce localized inflammatory responses. Treatment of activated endothelium with heparinase inhibits leukocyte rolling, adhesion and extravasation. Most of the heparin and heparan sulfate on endothelial cell surfaces and in basement membranes is degraded by exposure to heparinase. In addition, immobilized chemokines, which are attached to heparin / heparan sulfate on activated endothelium are solubilized by heparinase digestion. Heparinase can be infused into the vascular system to inhibit accumulation of leukocytes in inflamed tissue and decrease damage resulting from localized inflammations. Targeting of heparinase to activated endothelium can be accomplished through localized administration and / or use of genetically engineered heparinase containing endothelium ligand-binding domains.

Description

[0001] This application is related to U.S. provisional application Ser. No. 60 / 004,622, filed 29 Sep. 1995, which is expressly incorporated herein by reference.FIELD OF THE INVENTION [0002] This invention is in the field of medical treatments and is directed to the use of heparinase enzyme as a treatment or prophylactic for reducing localized inflammatory responses. BACKGROUND OF INVENTION [0003] An inflammatory response is local response to cellular injury that is marked by capillary dilation, leukocytic infiltration, redness, heat, and pain and serves as a mechanism initiating the elimination of noxious agents and of damaged tissue. [0004] A generalized inflammatory response within a tissue occurs by the recruitment of leukocytes to the tissue. Destruction of bacteria, foreign materials and / or damaged cells occurs through phagocytosis and / or extracellular degranulation (secretion of degradative enzymes, antimicrobial proteins and myeloperoxidase, which forms superoxides from secre...

AI Technical Summary

Benefits of technology

This patent is about using heparinase enzymes to decrease inflammation in localized areas. These enzymes can be from various sources and are capable of degrading heparin and heparan sulfate molecules on the surface of endothelial cells and basement membranes. By doing so, the enzymes prevent leukocytes from interacting with the cells and rolling on the surface, which can lead to inflammation. The patent also mentions that the heparinase enzymes can be targeted to specific cell types or organs, which can increase their effectiveness while reducing the amount of enzyme needed and minimizing potential side-effects. Overall, this patent provides a novel approach for treating inflammation and reducing tissue damage.

Problems solved by technology

While most localized inflammatory responses are beneficial, harmful inflammatory responses can occur.

Many harmful inflammatory responses also involve accumulation of leukocytes within a tissue.

This accumulation results in the destruction of viable cells and tissue.

In addition to damaging tissue, these responses are detrimental to, or debilitating for, the afflicted individual.

Because of difficulty in distinguishing regions of heparin and heparan sulfate on the same carbohydrate chain, little data exists on the binding preference of chemokines for either heparin or heparan sulfate moieties.

The antibodies interfere with the function of the adhesion molecules and block or reduce leukocyte recruitment.

The presence of soluble chemokine can interfere with adhesion and migration along a bound chemokine gradient.

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