Shapiro Fb

Involvement of thrombin in activation of heparin secretion by mast cells in immobilization stress in rats

Activation of heparin secretion by connective tissue mast cells under conditions of immobilization stress is determined by activation of the sympathoadrenal system, secretion of adrenocorticotropic hormone, and possible generation of thrombin. Generation of thrombin in the blood under these conditions is confirmed by a significant drop in the proenzyme protein C concentration by 23%, a decrease in the activity of factor V (substrate of protein C) by 36%, and prolongation of activated partial thromboplastin time by 40%. It is shown that 30-min immobilization leads to a 3-fold depletion of the heparin pool in mast cells. Intravenous injection of hirudin, a specific thrombin inhibitor, before immobilization slightly diminishes the stimulating effect of stress on heparin secretion. These data suggest that apart from catecholamines and adrenocorticotropic hormone, thrombin generated in the bloodstream during stress also markedly contributes to activation of heparin secretion by mast cells.

Role of adrenocorticotropic hormone in the activation of heparin secretion by mast cells in stressed rats

A morphometric analysis of mast cell populations in the subcutaneous tissue and mesentery from rats demonstrated stimulation of heparin secretion by adrenocorticotropic hormone. Thirty minutes after the administration of this hormone to unstressed rats, the functional stutus of mast cells did not differ from that of such cells from rats stressed by being immobilized for 30 min after receiving physiological saline instead of the hormone. In contrast, the 30-minute immobilization failed to elicit an adequate secretory response from the mast cells of rats in which the release of adrenocorticotropic hormone had been blocked by dexamethasone.

Incorporation of35S-heparin into rat mast cells and its release into the blood stream

Despite the extensive clinical use of heparin many aspects of its storage, site of synthesis, and processes of release remain unexplained. In the opinion of most investigators, heparin is released by exocytosis from the mast cells, its principal producers. However, there is no general agreement regarding the role of heparin in mast cells in the regulation of hemostasis. For instance, as well as the data published by Hatanaka [8] and Kitamura [ii], explaining the tendency toward thrombus formation in W/W v mice by their inability to produce heparin as a result of a mast cell deficiency, Marcum [14] is doubtful about the role of the heparin of mast cells in the maintenance of the anticoagulant potential of the blood.

Знaчeниe AКTГ для пroцecca oбraзoвaния кomплeкcныч coeдинeний гeпarинa в кroви пrи иmmoбилизaциoннom cтrecce

Abstract Under stress condition due to 30 min immobilization the total non-enzymatic fibrinolytic activity in rats is increased 4-fold, its proportion in the overall fibrinolytic activity of blood plasma being increased 1,5-fold. After pretreatment with ACTH (5–15 units) the same stress leads to more significant increase of non-enzymatic fibrinolysis which is 2,5 times higher than that in the absence of ACTH. The activity of fibrinogenheparin, epinephrineheparin, plasminogenheparin and plasminheparin complexes is increased 1,5–2,5 fold. ACTH induced a more efficient formation of heparin complexes also in the absence of stress. Its action is revealed in the course of 24 hours. Under blocked ACTH secretion as a result of DOCA treatment immobilization stress does not followed by increase of complex formation. The effect of ACTH on the formation of heparin complexes is mediated by stimulation of the adrenal cortex and by an increase in the corticosteroid level in the organism. Evidence of this has been produced from experiments on rats using ACTH treatment at different intervals after adrenalectomy. During first 24 hours after adrenalectomy when the additional cortical tissue is yet not active the injection of ACTH does not intensify heparin complexes formation. In 96 hours after adrebalectomy additional cortical tissue already responds to ACTH and accordingly stress after pretreatment with ACTH results in a greater increase of non=enzymatic fibrinolytic activity than that without ACTH.