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Contribution of the fibrinolytic pathway to hematopoietic regeneration
Author(s) -
Heissig Beate,
Ohki Makiko,
Ishihara Makoto,
Tashiro Yoshihiko,
Nishida Chiemi,
Gritli Ismael,
Rosenkvist Jeanette,
Hattori Koichi
Publication year - 2009
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21897
Subject(s) - haematopoiesis , plasmin , stromal cell , microbiology and biotechnology , stem cell , bone marrow , regeneration (biology) , hematopoietic stem cell , stromal cell derived factor 1 , matrix metalloproteinase , proteases , biology , stem cell factor , cxcr4 , immunology , chemistry , cancer research , inflammation , biochemistry , chemokine , enzyme
Hematopoietic stem cells (HSCs) can differentiate and proliferate in response to hematopoietic stress (e.g., myelosuppression, infections, and allergic reactions), thereby ensuring a well‐regulated supply of mature and immature hematopoietic cells within the circulation and prompt adjustment of blood cell levels within normal ranges. The recovery of tissues and organs from hematopoietic stress (e.g., myelosuppression or ionizing irradiation) is dependent on two cell types: resident HSCs which repopulate the bone marrow (BM) cavity, and stromal cells. BM regeneration critically depends on the release of soluble factors from cells such as stromal cells, a process regulated by proteases. Two proteolytic systems, the fibrinolytic system and the matrix metalloproteinases (MMPs), have recently been shown to be involved in this process (Heissig B, 2007, Cell Stem Cell 1: 658–670). The plasminogen/plasmin system is mostly recognized for its fibrinolytic activity, but it is also involved in processes such as cell invasion, chemotaxis, growth factor activity modulation, and tissue remodeling. This review focuses on the role of plasmin and its activators as key players in controlling the hematopoietic stress response after myelosuppression (hematopoietic regeneration). Aspects of plasmin regulation, especially regulation of its ability to activate MMPs and the functional consequences of this enzyme activation, such as plasmin‐mediated release of biologically relevant cytokines from the matrix and cell surfaces, will be discussed. J. Cell. Physiol. 221: 521–525, 2009. © 2009 Wiley‐Liss, Inc.