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Neutrophil gelatinase B and chemokines in leukocytosis and stem cell mobilization.
Starckx, S; Van den Steen, P E; Wuyts, A; Van Damme, J; Opdenakker, G.
Afiliação
  • Starckx S; Laboratory of Molecular Immunology, Rega Institute, University of Leuven, Belgium.
Leuk Lymphoma ; 43(2): 233-41, 2002 Feb.
Article em En | MEDLINE | ID: mdl-11999552
ABSTRACT
Leukocytosis is a physiopathological mechanism primarily to combat infections, whereas stem cell mobilization is induced for therapeutical purposes. Both processes are dependent on the balance between leukocyte and stem cell retention and mobilization. The retention is mediated by the specific architecture of the bone marrow, adhesion molecules and the production of chemokines in the bone marrow, which attract escaped immature cells to the marrow. Mobilization is the effect of the action of "peripheral" chemokines, such as interleukin-8 (IL-8 or CXCL8) and the remodeling of the matrix and basement membranes by matrix enzymes, such as gelatinase B (MMP-9). Recent studies lead to the conclusion that neutrophils, IL-8/CXCL8 and gelatinase B/MMP-9 play control roles in leukocytosis and stem cell mobilization. Neutrophils are the predominant circulating leukocyte type and IL-8/CXCL8 is the major neutrophil chemoattractant in humans. Gelatinase B and no gelatinase A is rapidly released from prestored granules after activation of neutrophils by IL-8/CXCL8. Moreover, neutrophils do not produce TIMP-1 and can chemically activate latent progelatinase B. Activated gelatinase B catalyses the aminoterminal truncation of IL-8/CXCL8 into a tenfold more potent chemokine. This implies that, when IL-8/CXCL8 appears in the circulation, the bone marrow is instructed to release neutrophils and concomitantly stem cells. These studies suggest that IL-8/CXCL8 and gelatinase B/MMP-9 are targets for the modulation of stem cell mobilization.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Mobilização de Células-Tronco Hematopoéticas / Leucocitose / Neutrófilos Limite: Animals / Humans Idioma: En Revista: Leuk Lymphoma Ano de publicação: 2002 Tipo de documento: Article
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Mobilização de Células-Tronco Hematopoéticas / Leucocitose / Neutrófilos Limite: Animals / Humans Idioma: En Revista: Leuk Lymphoma Ano de publicação: 2002 Tipo de documento: Article