1. Role of matrix metalloproteinases 2 and 9, toll-like receptor 4 and platelet-leukocyte aggregate formation in sepsis-associated thrombocytopenia.
- Author
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Larkin CM, Hante NK, Breen EP, Tomaszewski KA, Eisele S, Radomski MW, Ryan TA, and Santos-Martinez MJ
- Subjects
- Blood Platelets enzymology, Blood Platelets metabolism, Case-Control Studies, Female, Humans, Leukocytes enzymology, Leukocytes metabolism, Male, Middle Aged, Platelet Activation physiology, Platelet Count, Shock, Septic enzymology, Shock, Septic pathology, Thrombocytopenia enzymology, Thrombocytopenia pathology, Blood Platelets pathology, Leukocytes pathology, Matrix Metalloproteinase 2 blood, Matrix Metalloproteinase 9 blood, Shock, Septic blood, Thrombocytopenia blood, Toll-Like Receptor 4 blood
- Abstract
Background: The development of thrombocytopenia in sepsis is a poor prognostic indicator associated with a significantly increased mortality risk. Mechanisms underlying this phenomenon remain to be clearly elucidated. Matrix metalloproteinases (MMPs) are enzymes that regulate the turnover of the extra-cellular matrix. MMP-2 is recognised as a platelet agonist with MMP-9 proposed as an inhibitor of platelet activation. The existence of MMP-9 in platelets is a subject of debate. There is limited evidence thus far to suggest that toll-like receptor 4 (TLR-4) and platelet-leukocyte aggregate (PLA) formation may be implicated in the development of sepsis-associated thrombocytopenia., Objectives: To investigate whether MMP -2/-9, toll-like receptor 4 (TLR-4) or platelet-leukocyte aggregate (PLA) formation are implicated in a decline in platelet numbers during septic shock., Methods: This was an observational study which recruited healthy controls, non-thrombocytopenic septic donors and thrombocytopenic septic donors. MMP-2, MMP-9 and TLR-4 platelet surface expression as well as PLA formation was examined using flow cytometry. In addition MMP-2 and MMP-9 were examined by gelatin zymography and enzyme-linked immunosorbent assay (ELISA) using a 3 compartment model (plasma, intraplatelet and platelet membrane)., Results: There was no difference found in MMP-2, MMP-9 or TLR-4 levels between non-thrombocytopenic and thrombocytopenic septic donors. PLA formation was increased in thrombocytopenic patients. MMP-9 was detected in platelets using flow cytometry, gelatin zymography and ELISA techniques., Conclusions: Platelet consumption into PLAs may account for the development of thrombocytopenia in septic shock. MMP-9 is found in platelets and it is upregulated during septic shock.
- Published
- 2018
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