Advances in Neutrophil Biology: Clinical Implications

doi:10.1378/chest.08-0422

Chest

Volume 134, Issue 3, September 2008, Pages 606-612

https://doi.org/10.1378/chest.08-0422 Get rights and content

Many lung diseases are characterized by neutrophil-dominated inflammation; therefore, an understanding of neutrophil function is of considerable importance to respiratory physicians. This review will focus on recent advances in our understanding of how neutrophils are produced, how these cells leave the circulation, the molecular events regulating neutrophil activation and, ultimately, how these cells die and are removed. The neutrophil is now recognized as a highly versatile and sophisticated cell with significant synthetic capacity and an important role in linking the innate and adaptive arms of the immune response. One of the key challenges in conditions such as COPD, bronchiectasis, cystic fibrosis, and certain forms of asthma is how to manipulate neutrophil function in a way that does not compromise antibacterial and antifungal capacity. The possession by neutrophils of a unique repertoire of surface receptors and signaling proteins may make such targeted therapy possible.

Section snippets

Role of the Neutrophil in Respiratory Disease

Many airway diseases including COPD, bronchiectasis, bronchiolitis, and cystic fibrosis are characterized by neutrophil infiltration of the airway wall. Likewise, neutrophils are believed to play a fundamental role in acute lung injury (ALI)/ARDS and many of the vasculitides. Considerable observational and experimental data support an association between neutrophils and the severity and progression of the above airways diseases; for example, in COPD neutrophils have been shown to be the most

Conclusions

Our understanding of neutrophil biology, in particular the molecular and cellular mechanisms responsible for their formation and release from the bone marrow, their recruitment, priming and activation within inflamed tissues, and the events resulting in their removal have increased substantially over recent years. The view of the neutrophil as a short-lived, synthetically inert, and rather “monochromatic” cell with limited biodiversity is clearly no longer tenable. The unique transcriptome and

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The authors' laboratory is funded by the Wellcome Trust, Asthma-UK, MRC, Papworth Hospital, Cambridge NIHR Biomedical Research Centre and the British Lung Foundation.

The authors have no conflicts of interest relevant to this article to disclose.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

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Chest

Translating Basic Research Into Clinical PracticeAdvances in Neutrophil Biology: Clinical Implications

Section snippets

Role of the Neutrophil in Respiratory Disease

Conclusions

J Allergy Clin Immunol

Chest

J Allergy Clin Immunol

Blood

Immunity

Lancet

Chest

Trends Immunol

Blood

Blood

Biochem Biophys Res Commun

Remodelling and AHR but not cellular inflammation persist after allergen challenge in asthma

Am J Respir Crit Care Med

Neutrophils in asthma

Curr Allergy Asthma Rep

Neutrophil-derived elastase induces TGF-β1 secretion in human airway smooth muscle via NF-κB pathway

Am J Respir Cell Mol Biol

Mouse neutrophilic granulocytes express mRNA encoding the macrophage colony-stimulating factor receptor (CSF-1R) as well as many other macrophage-specific transcripts and can transdifferentiate into macrophages in vitro in response to CSF-1

J Leukoc Biol

Sputum chemotactic activity in chronic obstructive pulmonary disease: effect of α1-antitrypsin deficiency and the role of leukotriene B4 and interleukin 8

Thorax

Comparison of neutrophil and capillary diameters and their relation to neutrophil sequestration in the lung

J Appl Physiol

Neutrophil cytoskeletal rearrangements during capillary sequestration in bacterial pneumonia in rats

Am J Respir Crit Care Med

Getting to the site of inflammation: the leukocyte adhesion cascade updated

Nat Rev Immunol

Effects of CD18 deficiency on the emigration of murine neutrophils during pneumonia

J Immunol

RhoG regulates endothelial apical cup assembly downstream from ICAM1 engagement and is involved in leukocyte trans-endothelial migration

J Cell Biol

Venular basement membranes contain specific matrix protein low expression regions that act as exit points for emigrating neutrophils

J Exp Med

Central role for G protein-coupled phosphoinositide 3-kinase γ in inflammation

Science

Translating Basic Research Into Clinical Practice
Advances in Neutrophil Biology: Clinical Implications

Sputum chemotactic activity in chronic obstructive pulmonary disease: effect of α₁-antitrypsin deficiency and the role of leukotriene B₄ and interleukin 8