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The Role of Innate Immunity in Trafficking of Hematopoietic Stem Cells—An Emerging Link Between Activation of Complement Cascade and Chemotactic Gradients of Bioactive Sphingolipids

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Book cover Current Topics in Innate Immunity II

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 946))

Abstract

Hematopoietic stem and progenitor cells (HSPCs) circulate under steady-state conditions at detectable levels in peripheral blood (PB). The phenomenon of enforced release of HSPCs from BM into PB is called mobilization and may be envisioned as a danger-sensing response mechanism triggered by hypoxia or mechanical- or infection-induced tissue damage and is a part of stress response. It is unquestionable that the a-chemokine stromal derived factor-1 (SDF-1)—CXCR4 axis plays crucial role in retention of HSPCs in BM. However, all factors that direct mobilization of HSPCs into PB and homing back to the BM or their allocation to damaged organs are not characterized very well. In this chapter we will present mounting evidence that elements of innate immunity such as complement cascade (CC) cleavage fragments (e.g., C3a and C5a), granulocytes, generation of membrane attack complex (MAC) together with sphingosine-1 phosphate (S1P) orchestrate HSPC mobilization. On other hand some other bioactive lipids e.g., ceramide-1-phosphate (C1P) that is released from damaged/“leaky” cells in BM after myeloablative conditioning for transplant may play an opposite important role in homing of HSPCs to BM. Finally, the chemotactic activity of all chemoattractants for HSPCs including SDF-1, S1P and C1P is enhanced in presence of CC cleavage fragments (e.g., C3a) and MAC that is a final product of CC activation.

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Acknowledgments

This work was supported by NIH R01 DK074720, Stella and Henry Endowment and EU structural funds, Innovative Economy Operational Program POIG.01.01.01-00-109/09-01, and the Henry M. and Stella M. Hoenig Endowment to MZR.

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Authors and Affiliations

  1. Stem Cell Biology Program at the James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA

    Mariusz Z. Ratajczak, ChiHwa Kim, Wan Wu, Dong Myung Shin, Ewa Bryndza, Magda Kucia & Janina Ratajczak

  2. Department of Physiology, Pomeranian Medical University, Szczecin, Poland

    Mariusz Z. Ratajczak & Ewa Bryndza

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  1. Mariusz Z. Ratajczak
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  7. Janina Ratajczak
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Correspondence to Mariusz Z. Ratajczak .

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Editors and Affiliations

  1. Department Of Pathology Laboratory Of, Medicine, University Of Pennsylvania, Johnson Pavilion 410, Philadelphia, 19104, Pennsylvania, USA

    John D. Lambris

  2. Health Sciences Center, University of Louisville, Louisville, 40292, Kentucky, USA

    George Hajishengallis

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© 2012 Springer Science+Business Media, LLC

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Ratajczak, M.Z. et al. (2012). The Role of Innate Immunity in Trafficking of Hematopoietic Stem Cells—An Emerging Link Between Activation of Complement Cascade and Chemotactic Gradients of Bioactive Sphingolipids. In: Lambris, J., Hajishengallis, G. (eds) Current Topics in Innate Immunity II. Advances in Experimental Medicine and Biology, vol 946. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-0106-3_3

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