1997
DOI: 10.1046/j.1365-2141.1997.3293146.x
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The production of tissue inhibitors of metalloproteinases (TIMPs) in megakaryopoiesis: possible role of platelet‐ and megakaryocyte‐derived TIMPs in bone marrow fibrosis

Abstract: Summary.We quantified tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in serum and plasma in normal control subjects and patients with a low or high platelet count, using one-step sandwich enzyme immunoassays. The serum levels of TIMP-1 and TIMP-2 were 101 . 1 Ϯ 13 . 3 ng/ml, and 82 . 7 Ϯ 26 . 3 ng/ml, respectively, in normal subjects. In patients with an elevated platelet count, such as in essential thrombocytosis, polycythaemia vera, and myelofibrosis, serum levels of TIMP-1 and TIMP-2 were 351 . 6… Show more

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Cited by 61 publications
(36 citation statements)
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“…This finding can be explained by the fact that PMF patients without significant fibrosis and leukocytosis (albeit being a very small group in this study) were likely to be JAK2 negative (table 2), perhaps representing an earlier prefibrotic cellular phase that may be associated with low TIMP levels. TIMP-1 serum levels have previously been shown to be related to platelet number and function, thus raising the question of whether its concentration is elevated in thrombocytosis and in conditions with increased platelet activation [19]. In our study, increased TIMP-1 levels, regardless of platelet counts, were found in all patients, with the highest levels for PMF recorded in the JAK2-positive patients.…”
Section: Discussionsupporting
confidence: 55%
See 1 more Smart Citation
“…This finding can be explained by the fact that PMF patients without significant fibrosis and leukocytosis (albeit being a very small group in this study) were likely to be JAK2 negative (table 2), perhaps representing an earlier prefibrotic cellular phase that may be associated with low TIMP levels. TIMP-1 serum levels have previously been shown to be related to platelet number and function, thus raising the question of whether its concentration is elevated in thrombocytosis and in conditions with increased platelet activation [19]. In our study, increased TIMP-1 levels, regardless of platelet counts, were found in all patients, with the highest levels for PMF recorded in the JAK2-positive patients.…”
Section: Discussionsupporting
confidence: 55%
“…MMP activity is regulated by tissue inhibitors of metalloproteases (TIMPs) [16,17]: TIMP-1 inhibits MMP-9, while TIMP-2 regulates MMP-2 activation and function [18]. Megakaryocytes and platelets are rich sources of TIMPs [19], which also stimulate the proliferation of bone marrow fibroblasts resulting in speculative conclusions regarding their role in the development of bone marrow fibrosis.…”
Section: Introductionmentioning
confidence: 99%
“…A leakage of MMPs from other tissues such as atherosclerotic plaques cannot be excluded but is very difficult to verify in humans. The sources of TIMP-1 and TIMP-2 may be several, including platelets, smooth muscle cells and fibroblasts (161,164,165). Our present findings do not provide any evidence that leukocytes are major producers of TIMPs.…”
Section: Serum and Plasma Levels Of Mmps And Timpscontrasting
confidence: 49%
“…The results of our studies are in accordance with the observations presented below. The studies by other authors indicated that the TIMP-1 protein occurs in α granules of platelets [33,34], which indicates that these cells can determine the protein level in plasma and serum [35]. Possible participation of the platelet count in TIMP-1 protein secretion was observed in patients with CRC [36,37].…”
Section: Discussionmentioning
confidence: 92%