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Review
. 2012 May;46(5):566-72.
doi: 10.1165/rcmb.2011-0392TR. Epub 2012 Feb 9.

Role of chemokines in the pathogenesis of acute lung injury

Madhav Bhatia  1 , Rachel L Zemans, Samithamby Jeyaseelan
Affiliations
Review

Role of chemokines in the pathogenesis of acute lung injury

Madhav Bhatia et al. Am J Respir Cell Mol Biol. 2012 May.

Abstract

Acute lung injury (ALI) is due to an uncontrolled systemic inflammatory response resulting from direct injury to the lung or indirect injury in the setting of a systemic process. Such insults lead to the systemic inflammatory response syndrome (SIRS), which includes activation of leukocytes-alveolar macrophages and sequestered neutrophils-in the lung. Although systemic inflammatory response syndrome is a physiologic response to an insult, systemic leukocyte activation, if excessive, can lead to end organ injury, such as ALI. Excessive recruitment of leukocytes is critical to the pathogenesis of ALI, and the magnitude and duration of the inflammatory process may ultimately determine the outcome in patients with ALI. Leukocyte recruitment is a well orchestrated process that depends on the function of chemokines and their receptors. Understanding the mechanisms that contribute to leukocyte recruitment in ALI may ultimately lead to the development of effective therapeutic strategies.

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Figures

Figure 1.
Figure 1.
Polymorphonuclear cell (PMN) chemotaxis into the lung in acute lung injury (ALI). Chemokines are secreted at the site of inflammation by resident tissue cells, leukocytes, and cytokine-activated endothelial and epithelial cells. Chemokines are locally retained by matrix heparan sulfate proteoglycans establishing a chemokine gradient surrounding the inflammatory stimulus. PMNs roll over the endothelium in a selectin-mediated process. Chemokine signaling activates leukocyte integrins, leading to firm adherence and extravasation. The PMNs then pass out of the blood vessel and move up the concentration gradient of the chemotactic peptides toward the site of inflammation. The Duffy antigen receptors for chemokines (DARC) functions as a sink, removing the chemokines from circulation and thus helping to maintain the tissue blood stream gradient. In ALI, the capillary endothelium and alveolar epithelium have separate injuries. Macrophages are recruited to the lung by chemokine gradients in ALI and play a role in the pathogenesis and resolution of lung injury. Activated alveolar macrophages release TNF-α and IL-1β and, in response to this, other cells of the alveolar environment produce CC and CXC chemokines, which, in turn, activate the inflammatory cascade, resulting in PMN migration into the lungs (reproduced by permission from Ref. 2).
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