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Review
. 2008 Sep;134(3):606-612.
doi: 10.1378/chest.08-0422.

Advances in neutrophil biology: clinical implications

Andrew S Cowburn  1 , Alison M Condliffe  1 , Neda Farahi  1 , Charlotte Summers  1 , Edwin R Chilvers  2
Affiliations
Review

Advances in neutrophil biology: clinical implications

Andrew S Cowburn et al. Chest. 2008 Sep.

Abstract

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.

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Figures

Figure 1
Figure 1
Neutrophil activation states. When neutrophils adhere to biological surfaces (eg, fibronectin, collagen) or are exposed to inflammatory mediators such as lipopolysaccharide or IL-8, they become “primed” or hyperresponsive to subsequent activating stimuli, acquiring the capacity to exhibit maximal degranulation and respiratory burst responses and enhanced cytokine and lipid mediator release. Agents that prime neutrophils usually also extend their lifespan by inhibiting apoptosis. The normal age-dependent apoptotic program intrinsic to the neutrophil can be accelerated by ingestion of bacterial pathogens such as Escherichia coli or S aureus (which may promote resolution of bacterial inflammation) or by exposure of these cells to tumor necrosis factor (TNF)α or Fas-ligand (FasL).
Figure 2
Figure 2
NET formation. Neutrophils exposed to activating stimuli such as opsonized bacteria become activated and may loose their nuclear integrity, leading to the discharge of granule contents adherent to chromatin strands. These web-like structures may trap and kill bacteria or fungi even after the death of the parent cell.
Figure 3
Figure 3
Neutrophil fate and function in health and disease. Normal physiology: neutrophils produced in the bone marrow circulate in the bloodstream prior to removal by the bone marrow, or by the liver and spleen (inset is a gamma camera image showing the distribution of 111In tropolone labeled neutrophils in a healthy volunteer at 24 h, depicting the extravascular fate of these cells in the liver, spleen, and bone marrow). Fate during local and systemic inflammation: primed neutrophils undergo rheologic changes leading to retention in the lung microvasculature; such changes are reversible, and in the absence of a further activating stimulus the cells may return to the circulation. If a further activating input is received, the retained neutrophils migrate to the inflamed lung parenchyma to ingest and kill invading bacteria; this may promote apoptosis and the resolution of inflammation, with the apoptotic neutrophils being engulfed by resident macrophages. Conversely, the ingestion of certain bacteria (eg, noncapsulated H influenzae and certain strains of Streptococcus pyogenes) or excessive activation signals may lead to neutrophil necrosis and hence to tissue injury. It has been suggested that neutrophils may undergo transdifferentiation to other cell types (eg, macrophages) and participate in antigen presentation.
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