Inflammation: The Leukocyte Adhesion Cascade

Inflammation is a defense reaction caused by tissue damage or injury, characterized by redness, heat, swelling, and pain. The primary objective of inflammation is to localize and eradicate the irritant and repair the surrounding tissue. For the survival of the host, inflammation is a necessary and beneficial process. The inflammatory response involves three major stages: first, dilation of capillaries to increase blood flow; second, microvascular structural changes and escape of plasma proteins from the bloodstream; and third, leukocyte transmigration through endothelium and accumulation at the site of injury.

The leukocyte adhesion cascade is a sequence of adhesion and activation events that ends with extravasation of the leukocyte, whereby the cell exerts its effects on the inflamed site. At least five steps of the adhesion cascade are capture, rolling, slow rolling, firm adhesion, and transmigration. Each of these five steps appears to be necessary for effective leukocyte recruitment, because blocking any of the five can severely reduce leukocyte accumulation in the tissue. These steps are not phases of inflammation, but represent the sequence of events from the perspective of each leukocyte. At any given moment, capture, rolling, slow rolling, firm adhesion and transmigration all happen in parallel, involving different leukocytes in the same microvessels.

The roles of adhesion molecules in acute and chronic inflammation have been investigated using in vitro model systems and in vivo microcirculation studies. The ultimate goal of inflammation research is to develop methods to control inflammation by modulating or blocking leukocyte adhesion to the endothelium. These ideas developed by basic research contribute to contemporary research projects developing anti-inflammatory drugs. Anti-inflammatory agents function as blockers, suppressors, or modulators of the inflammatory response.

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Capture Rolling Slow Rolling Firm Adhesion Transmigration Chemoattractants Chemoattractants Endothelium Leukocyte Activation Selectins Integrins