Cytokine and estrogen stimulation of endothelial cells augments activation of the prekallikrein-high molecular weight kininogen complex: Implications for hereditary angioedema
Autor: | Kusumam Joseph, Allen P. Kaplan, Baby G. Tholanikunnel |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
medicine.medical_specialty Kininogen High-Molecular-Weight High-molecular-weight kininogen Plasmin Immunology Bradykinin 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine Human Umbilical Vein Endothelial Cells Immunology and Allergy Humans cardiovascular diseases HSP90 Heat-Shock Proteins Cells Cultured Urokinase Factor XII Estradiol Chemistry Tumor Necrosis Factor-alpha Prekallikrein Angioedemas Hereditary Estrogens Kallikrein Urokinase-Type Plasminogen Activator 030104 developmental biology Endocrinology 030228 respiratory system Tissue Plasminogen Activator Plasminogen activator inhibitor-2 circulatory and respiratory physiology medicine.drug Interleukin-1 |
Zdroj: | The Journal of allergy and clinical immunology. 140(1) |
ISSN: | 1097-6825 |
Popis: | Background When the prekallikrein-high molecular weight kininogen complex is bound to endothelial cells, prekallikrein is stoichiometrically converted to kallikrein because of release of heat shock protein-90 (Hsp90). Although bradykinin formation is typically initiated by factor XII autoactivation, it is also possible to activate factor XII either by kallikrein, thus formed, or by plasmin. Objective Because attacks of hereditary angioedema can be related to infection and/or exposure to estrogen, we questioned whether estrogen or cytokine stimulation of endothelial cells could augment release of Hsp90 and prekallikrein activation. We also tested release of profibrinolytic enzymes, urokinase, and tissue plasminogen activator (TPA) as a source for plasmin formation. Methods Cells were stimulated with agonists, and secretion of Hsp90, urokinase, and TPA was measured in the culture supernatants by ELISA. Activation of the prekallikrein-HK complex was measured by using pro-phe-arg-p-nitroanilide reflecting kallikrein formation. Results Hsp90 release was stimulated with optimal doses of estradiol, IL-1, and TNF-α (10 ng/mL) from 15 minutes to 120 minutes. TPA release was not augmented by any of the agonists tested but urokinase was released by IL-1, TNF-α, and thrombin (positive control), but not estrogen. Augmented activation of the prekallikrein-HK complex to generate kallikrein was seen with each agonist that releases Hsp90. Addition of 0.1% factor XII relative to prekallikrein-HK leads to rapid formation of kallikrein; factor XII alone does not autoactivate. Conclusions IL-1, TNF-α, and estrogen stimulate release of Hsp90 and augment activation of the prekallikrein-HK complex to generate kallikrein and bradykinin. IL-1 and TNF-α stimulate release of urokinase, which can convert plasminogen to plasmin and represents a possible source for plasmin generation in all types of hereditary angioedema, but particularly hereditary angioedema with normal C1 inhibitor with a factor XII mutation. Both kallikrein and plasmin activate factor XII; kallikrein is 20 times more potent on a molar basis. |
Databáze: | OpenAIRE |
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