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  • Review Article
  • Published:

Role of chemokines in the pathogenesis of asthma

Nature Reviews Immunology volume 1, pages 108–116 (2001)Cite this article

Key Points

  • Asthma is now thought to be an inflammatory disease, the severity of which is linked to the intensity of leukocyte recruitment into the lung. Chemokines are small cytokines that regulate the number, intensity and activation of leukocyte migration into the asthmatic airways. A number of chemokines have been identified in the airways during human asthmatic responses.

  • Chemokines in two distinct families (CxC and CC) now number upwards of ∼45 different members which have diverse and distinct functions during homeostasis and disease progression.

  • Six CxC and ten CC chemokine G-protein-coupled receptors have been identified which engage a number of chemokine ligands in a promiscuous manner, causing confusion as well as diverse options for therapeutic intervention.

  • It now appears that TH2 lymphocytes and eosinophils are the most important cell types that are associated with development of severe asthmatic disease. Identification of specific chemokines and receptors that are responsible for the migration of these cell populations into the airways are the focus of most discovery programs.

  • Animal models of asthma have identified a number of viable chemokine and chemokine receptor targets, the inhibition of which might substantially alter asthmatic disease progression.

  • Chemokines are important factors for directing specific leukocyte recruitment and activation, including degranulation of eosinophils, mast cells and neutrophils, as well as having the ability to direct the immune response. All of these aspects will need to be considered when investigating new methods for inhibiting chemokines to modulate disease progression.

Abstract

The prevalence of asthma has risen drastically in the last two decades, with a worldwide impact on health care systems. Although several factors contribute to the development of asthma, inflammation seems to be a common factor that leads to the most severe asthmatic responses. In the past decade, researchers have characterized a large group of chemotactic cytokines, also known as chemokines, which are implicated in asthmatic inflammation. These chemokines control and direct the migration and activation of various leukocyte populations. Targeting chemokines should lead to new ways of controlling the inflammatory asthmatic response.

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Figure 1: Phases of asthmatic responses.
Figure 2: Chemokine-induced migration of eosinophils in lungs.
Figure 3: TH2 cytokine-induced responses.
Figure 4: Differential expression of CCRs on TH subsets.

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Acknowledgements

I thank R. Kunkel for design of the original figures.

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Authors and Affiliations

  1. Department of Pathology, University of Michigan Medical School, 1301 Catherine Road, Ann Arbor, 48109-0602, Michigan, USA

    Nicholas W. Lukacs

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  1. Nicholas W. Lukacs
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DATABASES

LocusLink

CCL1

CCL2

CCL3

CCL5

CCL7

CCL11

CCL13

CCL17

CCL21

CCL22

CCL24

CCL26

CCR1

CCR2

CCR3

CCR4

CCR5

CCR7

CCR8

CxCL8

CxCR4

CxCL12

ERK

IL-4

IL-5

IL-13

STAT6

TGF-β

Glossary

DEGRANULATION

Release of mediators, proteases and so on from stored granules in the cytoplasm of mast cells, neutrophils, eosinophils or other leukocyte populations.

AIRWAY HYPERREACTIVITY

Physiologic measurement of the changes in airway resistance induced by a pharmacologic stimuli, such as methacholine.

OVA-INDUCED EOSINOPHILIA

Ovalbumin-induced animal model of allergic airway inflammation.

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Lukacs, N. Role of chemokines in the pathogenesis of asthma. Nat Rev Immunol 1, 108–116 (2001). https://doi.org/10.1038/35100503

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