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The chemokine system: redundancy for robust outputs

https://doi.org/10.1016/S0167-5699(99)01469-3Get rights and content

Abstract

Chemokines are redundant in their action on target cells and promiscuous in receptor usage. Moreover, certain cells concomitantly produce several chemokines with an overlapping spectrum of action. Here, Alberto Mantovani argues that such robustness provides a conceptual framework to understand these intriguing aspects of the chemokine system.

Section snippets

Redundancy, promiscuity and ‘polyspeirism'

The eponymous function of chemokines is chemotaxis for leukocytes. Schematically, CXC (or α) chemokines are active on polymorphonuclear neutrophils (PMNs) and T and B cells, whereas CC (or β) chemokines exert their action on multiple leukocyte subtypes, including monocytes, basophils, eosinophils, T cells, dendritic cells and natural killer (NK) cells, but they are generally inactive on PMNs. Eotaxins (CC) represent the chemokines with the most restricted spectrum of action, being active

Robustness of the chemokine system

Phagocytes play a central role in the fundamental functions of multicellular organisms, including tissue remodeling and defense. Among cells responding to chemokines, monocytes respond to the widest array of mediators, including virtually all CC chemokines, fractalkine (CX3C) and, under certain conditions, some CXC molecules. Under a variety of conditions, many of these mediators are produced in concert: for example, activated endothelium produces MIPs, MCPs, RANTES, fractalkine, and other

Concluding remarks

Robustness might be a common feature of many cytokine and growth factor networks and could be essential for their performance. Robust outputs of these cytokine networks may be retained to a sufficient extent, even if genetic or epigenetic alterations that affect the qualitative or quantitative properties of individual components occur.

Acknowledgements

This work is supported by Istituto Superiore di Sanità, Project AIDS CNR, special project Biotechnology, EC Biomed BMH4-98-2343 and Associazione Italiana per la Ricerca sul Cancro. I thank S. Sozzani, P. Allavena, A. Vecchi and M. Locati for helpful discussion and A. Palmiero and F. De Ceglie for help in the preparation of the manuscript. The CCL nomenclature was proposed by O. Yoshie and A. Zlotnik at the 1999 Keystone Symposium on chemokines.

References (39)

  • J.A. Hedrick et al.

    Curr. Opin. Immunol.

    (1996)
  • B.J. Rollins

    Blood

    (1997)
  • F. Sallusto et al.

    Immunol. Today

    (1998)
  • R. Bonecchi et al.

    Blood

    (1998)
  • A. Ben-Baruch et al.

    J. Biol. Chem.

    (1995)
  • R. Liu et al.

    Cell

    (1996)
  • M. Baggiolini

    Nature

    (1998)
  • R. Bonecchi et al.

    J. Exp. Med.

    (1998)
  • F. Sallusto et al.

    Science

    (1997)
  • P. Loetscher et al.

    Nature

    (1998)
  • D. D'Ambrosio et al.

    J. Immunol.

    (1998)
  • A. Sica et al.

    J. Exp. Med.

    (1997)
  • S. Sozzani et al.

    J. Exp. Med.

    (1998)
  • S. Sozzani et al.

    J. Immunol.

    (1998)
  • F. Sallusto et al.

    Eur. J. Immunol.

    (1998)
  • M.C. Dieu et al.

    J. Exp. Med.

    (1998)
  • N. Barkai et al.

    Nature

    (1997)
  • L. Hartwell

    Nature

    (1997)
  • T.J. Schall
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