Complement Split Product C5a Mediates the Lipopolysaccharide‐Induced Mobilization of Cfu‐S and Haemopoietic Progenitor Cells, But Not the Mobilization Induced By Proteolytic Enzymes

Molendijk, W.J.; Oudenaren, A. Van; Dijk, Hans van; Daha, Mohamed R.; Benner, R.

doi:10.1111/j.1365-2184.1986.tb00738.x

Cited by 11 publications

(13 citation statements)

References 17 publications

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“…We noticed that while C3 (C3a, desArg C3a) cleavage fragments increase the retention of HSPCs in BM, C5 (C5a, desArg C5a) cleavage fragments enhance the egress of HSPCs into PB. This was evidenced in mobilization studies performed in C3-and C5-deficient animals which revealed that C3-deficient mice are easy mobilizers and C5-deficient mice poor mobilizers (Molendijk et al 1986;Ratajczak et al 2004a;Reca et al 2003;Reca et al 2007). …”

Section: Pharmacological Mobilization Of Hspcsmentioning

confidence: 95%

“…Fms-like tyrosine kinase 3, KL, vascular endothelial growth factor [VEGF]), and small molecular CXCR4 receptor antagonists (e.g. AMD3100, T140) (Andrews et al 1994;Hattori et al 2001;King et al 2001;Laterveer et al 1995;Liles et al 2003;Mohle et al 1998;Molendijk et al 1986;Papayannopoulou et al 1997;Ratajczak et al 2004a;Reca et al 2003). To obtain more efficient and faster mobilization, some of these compounds could be combined together (e.g.…”

Section: Pharmacological Mobilization Of Hspcsmentioning

confidence: 99%

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Innate immunity: a key player in the mobilization of hematopoietic stem/progenitor cells

Lee

Ratajczak

2009

Arch. Immunol. Ther. Exp.

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The mobilization of hematopoietic stem/progenitor cells (HSPCs) from bone marrow into peripheral blood (PB) is still not fully understood. Different chemokines, cytokines, growth factors, and neurotransmitters have been described that facilitate this process. However, mounting evidence suggests that mobilization of HSPCs is a part of the immune response and is mediated by innate immunity. We discuss evidence showing that complement system cleavage fragments play a crucial role in both the retention and mobilization of HSPCs by modulating their responsiveness to stromal-derived growth factor-1 (SDF-1) gradient (by C3-derived anaphylatoxins) and by modulating the release of granulocytes into PB that subsequently facilitate the egress of HSPCs (by C5-derived anaphylatoxins).

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Section: Pharmacological Mobilization Of Hspcsmentioning

confidence: 95%

Section: Pharmacological Mobilization Of Hspcsmentioning

confidence: 99%

Innate immunity: a key player in the mobilization of hematopoietic stem/progenitor cells

Lee

Ratajczak

2009

Arch. Immunol. Ther. Exp.

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“…Mobilization through G-CSF is associated with a decrease in heparanase levels and a concomitant increase of MMP-9 and cathepsins [34]. The exact role of other proteins, such as complement [35] and the fibrinolysis/plasminogen [36] system, has not been elucidated yet.The same proteolytic G-CSF-induced mechanism is responsible for the degradation of VCAM-1, fibronectin, and OPN, leading to reduced cellular adhesion of HSC through their receptor VLA-4 to BM stroma [28, 37]. …”

Section: Mechanisms Of Hsc Mobilizationmentioning

confidence: 99%

Section: Mechanisms Of Hsc Mobilizationmentioning

confidence: 99%

New Insights in the Mobilization of Hematopoietic Stem Cells in Lymphoma and Multiple Myeloma Patients

Angelopoulou

Tsirkinidis

Boutsikas

et al. 2014

BioMed Research International

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Following chemotherapy and/or the administration of growth factors, such as granulocyte-colony stimulated factor (G-CSF), hematopoietic stem cells (HSC) mobilize from bone marrow to peripheral blood. This review aims to systematically present the structure of the HSC “niche” and elucidate the mechanisms of their mobilization. However, this field is constantly evolving and new pathways and molecules have been shown to contribute to the mobilization process. Understanding the importance and the possible primary pathophysiologic role of each pathway is rather difficult, since they share various overlapping components. The primary initiating event for the mobilization of HSC is chemotherapy-induced endogenous G-CSF production or exogenous G-CSF administration. G-CSF induces proliferation and expansion of the myelomonocytic series, which leads to proteolytic enzyme activation. These enzymes result in disruption of various receptor-ligand bonds, which leads to the disanchorage of HSC from the bone marrow stroma. In everyday clinical practice, CXC chemokine receptor-4 (CXCR4) antagonists are now being used as mobilization agents in order to improve HSC collection. Furthermore, based on the proposed mechanisms of HSC mobilization, novel mobilizing agents have been developed and are currently evaluated in preclinical and clinical studies.

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“…C5 deficient A/J and C5 -/- mice show poor granuloma formation needed for containment of the infection and instead show a pneumonitis. Macrophages secrete a C5 peptidase, which cleaves C5 into C5a and C5b [12]. The most potent anaphylatoxin of the complement system is C5a, the 14 kDa cleavage product of C5.…”

Section: Introductionmentioning

confidence: 99%

A defect in the synthesis of Interferon-γ by the T cells of Complement-C5 deficient mice leads to enhanced susceptibility for tuberculosis

et al. 2011

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Interferon-γ (IFNγ) plays a major role during host defense against Mycobacterium tuberculosis (Mtb). T cells produce IFNγ in response to IL-12 and IL-18 secreted from Mtb infected macrophages. IFNγ in turn, induces nitric oxide secretion in macrophages that kills Mtb. IFNγ knock-out mice are thus hyper-susceptible to tuberculosis. We reported earlier that Complement C5 deficient (C5-/-) congenic mice are more susceptible to tuberculosis and showed reduced IL-12 synthesis in their macrophages. Using C5-/- congenic mice that carry a deletion in the C5 gene and the wild type C5+/+ mice, we demonstrate here that, the C5-/-derived CD3+ T cells, have an additional defect in the synthesis of IFNγ. C5-/- T cells produced lower levels of IFNγ upon stimulation by antigen presenting cells (APCs) infected with Mtb or when stimulated directly with a combination of IL-12 and IL-18. The latter was in part due to a reduced phosphorylation of STAT-4 following IL-12/IL-18 stimulation. Addition of C5a peptide to IL-12/IL-18 partially restored STAT4 phosphorylation and IFNγ synthesis in C5-/- T cells indicating that IL-12/IL-18 mediated signaling within CD3+ T cells involves C5a peptide. Finally, C5-/- T cells derived from M.bovis BCG or Mtb infected mice showed a reduced expression of T-bet (T-box expressed in T cells) transcription factor, which correlated well with a reduced T cell secretion of IFNγ. Since T-bet mediated IFNγ synthesis facilitates Th1 expansion, C5-/- mouse derived T cells appear to have an intrinsic defect in the production of IFNγ, which is related to C5 deficiency and this may explain their increased susceptibility to infection with Mtb and BCG.

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Complement Split Product C5a Mediates the Lipopolysaccharide‐Induced Mobilization of Cfu‐S and Haemopoietic Progenitor Cells, But Not the Mobilization Induced By Proteolytic Enzymes

Cited by 11 publications

References 17 publications

Innate immunity: a key player in the mobilization of hematopoietic stem/progenitor cells

Innate immunity: a key player in the mobilization of hematopoietic stem/progenitor cells

New Insights in the Mobilization of Hematopoietic Stem Cells in Lymphoma and Multiple Myeloma Patients

A defect in the synthesis of Interferon-γ by the T cells of Complement-C5 deficient mice leads to enhanced susceptibility for tuberculosis

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