Mast Cells Heparin — New Information on the Old Component (Review)

Abstract

Mast cells (MC) are widely distributed throughout the body of animals and humans, mainly in barrier tissues. This review provides new information on the hematopoietic origin of MCs from early erythromyeloid progenitors (EMPs), late EMPs, and definitive hematopoietic stem cells. As well as information on the maturation of MSs and heparin synthesis already in the embryonic period. Many physiological functions of MCs are determined by the properties of heparin, which forms the basis of the matrix of granules, since the heparin molecule is a strong polyanion, capable to forming complexes with many biologically active substances and regulating their properties. In a new hypothesis about the participation of MCs in pathological processes, it is assumed that this is due to the depletion of the heparin pool. In such cases, injections of exogenous heparin can help replenish MCs heparin stores. As a result of the restoration of the physiological functions of MCs and the action of exogenous heparin, the pathological process will be converted into an adaptive one. In clinical practice, unfractionated heparin (UFH) obtained from natural sources and low molecular weight heparin (LMWH) obtained by the biochemical route are used. Most often, UFH and LMWH are used in the clinic only as anticoagulants. The worldwide spread of a disease named COVID-19 in 2020 showed that UFH and LMWH are multifunctional drugs that have saved many people. The pandemic caused by COVID-19 has been an unprecedented social and health emergency worldwide. Depression, anxiety and post-traumatic stress disorder (PTSD) have been reported in populations of many countries. This review provides new information on experimental studies on the successful treatment of pathology with low doses of UFH in modeling PTSD in animals. Consequently, heparin can be considered as a promising multifunctional drug for effective pharmacological correction of comorbid diseases under the influence of extreme factors.

Horizons of Heparin Therapy in COVID-19 and Pandemic-Related Diseases

“…Heparin is secreted into the extracellular space, and does not enter the bloodstream under physiological conditions. It is used locally, performing the functions of a non-specific adaptogen, protecting the body from toxins, various parasites (including viruses and bacteria), as well as regulator of intercellular interactions [ 7 ]. The anticoagulant properties of heparin become significant under the influence of any external or internal factors leading to the threat of microcirculation disorders, stasis, thrombosis, etc.…”

“…Heparin enters the bloodstream already in the early stages of pathological processes, where it prevents damage of the vascular endothelium by binding (complexation) and inactivation of biologically active substances. It also reduces the endothelial adhesiveness, restoring the altered membranes electronegative potential, and inhibits the activation of cellular and plasma coagulation factors [ 7 , 8 ]. Thus, endogenous heparin is a polyfunctional biologically active mast cell mediator, while the anticoagulant effect is only one of its effects.…”

“…Thus, endogenous heparin is a polyfunctional biologically active mast cell mediator, while the anticoagulant effect is only one of its effects. By preventing thrombosis, heparin promotes the restoration of the habitat of surrounding cells, providing them with a full-fledged delivery of trophic and energetic substances [ 7 , 8 ].…”

“…A high degree of molecule sulfation provides a high negative charge and a high degree of binding with other biologically active substances, thus changing their properties. Due to the great similarity with endogenous heparin, UFH reveals multifunctional qualities [ 7 , 8 ].…”

“…Low-molecular-weight heparins (LMWHs) represent a class of variously depolymerized UFH derivatives designed to reduce their side effects. Each type of LMWHs has a pronounced cumulative effect and pharmacological profile, therefore, the information about the properties of one LMWH cannot be extrapolated to others [ 7 , 8 , 9 ].…”