Polymorphonuclear leukocytes (PMNs, or neutrophils) are positioned in the microvasculature of the lung to respond immediately to inflammatory stimuli. They sequester in the lung capillaries through unique hemodynamic and geometric properties of the pulmonary microvasculature, as well as changes in their biophysical properties during activation. In contrast to the systemic circulation, the pulmonary microvasculature has the capacity to shunt blood flow away from inflamed areas through vasoconstriction, which acts to limit the extent of PMN emigration into the airspaces. Due to these unique features of the pulmonary circulation, PMN migration in acute pulmonary inflammation is not always dependent on the typical multistep process of selectin-mediated rolling transitioning to chemokine-activated integrin-dependent arrest on Ig-CAMs. PMNs can cause extensive damage to the lung in a variety of infectious and toxicological inflammatory disorders. This is accomplished by their production of reactive oxygen species (ROS) and release of granule components upon activation. Experimental models suggest that repetitive pulmonary inflammation and accompanying epithelial injury exacerbate the inflammatory cascade and enhance the extent of pulmonary inflammation and epithelial injury in subsequent cycles. However, there is also evidence that PMNs play an important role in removing injured pulmonary cells to enhance repair of the lung. The mechanisms utilized by PMNs to target injured cells and selectively kill them or cause their junctional detachment in the absence of parenchymal derangement are just beginning to be understood. Clearly this beneficial action of the PMN occurs only in mild toxicological injury to the lung since it appears to be a dose-dependent toxicological response with mild injury resulting in low to moderate PMN emigration, while severe injury is associated with robust PMN recruitment, degranulation, and reactive oxygen elaboration.
|Original language||English (US)|
|Title of host publication||Respiratory Toxicology|
|Number of pages||13|
|State||Published - Aug 12 2010|
- Blood flow
- Oxidant stress
ASJC Scopus subject areas