Initial interaction of leukocytes within the microvasculature: deformability, adhesion, and transmigration.

: Sequestration and migration of neutrophils in response to acute inflammation involve sequential steps, including delivery of cells to the site of inflammation, sequestration within the microvasculature, adhesion, and transmigration out of the vascular space into interstitial tissues. Soluble mediators released in the inflammatory milieu and into the circulation cause profound changes in leukocytes, both circulating and sequestered, as well as in the vascular endothelium promoting this leukocyte sequestration and adhesion. Although common mechanisms exist regulating leukocyte sequestration in the systemic and pulmonary microcirculations, important differences are also apparent. Alterations in cellular deformability appear to be most important in sequestration of neutrophils in the pulmonary capillaries because of the unique geometric and hydrodynamic conditions in the pulmonary microcirculation. Neutrophils undergo dramatic morphologic and functional alteration not only during these processes, but as a consequence of them. This can lead to the release of a substantive armamentarium of toxic mediators from activated leukocytes, including reactive oxygen species via the oxidative burst and secretion of proteolytic enzymes contained within granules. These toxic compounds can have profound and detrimental effects on host tissues, leading to pulmonary dysfunction and multiorgan failure.