Table 3.3 ). Macrophages are discussed in more detail later, in the context of chronic inflammation. These leukocytes ingest and destroy bacteria and other microbes, as well as necrotic tissue and foreign substances. Macrophages also produce growth factors that aid in repair. A price that is paid for the defensive potency of leukocytes is that, when strongly activated, they may induce tissue damage and prolong inflammation, because the leukocyte products that destroy microbes and help “clean up” necrotic tissues can also produce “collateral damage” of normal host tissues. When there is systemic activation of inflammation, as may occur when there is invasion of the bloodstream by bacteria, the resulting systemic inflammatory response may even be lethal.
The journey of leukocytes from the vessel lumen to the tissue is a multistep process that is mediated and controlled by adhesion molecules and cytokines. Leukocytes normally flow rapidly in the blood, and in inflammation, they have to be stopped and then brought to the offending agent or the site of tissue damage, outside the vessels. This process can be divided into phases, consisting first of adhesion of leukocytes to endothelium at the site of inflammation, then transmigration of the leukocytes through the vessel wall, and movement of the cells toward the offending agent. Different molecules play important roles in each of these steps (
Fig. 3.4
Leukocyte Adhesion to Endothelium
When blood flows from capillaries into postcapillary venules, circulating cells are swept by laminar flow against the vessel wall. Red cells, being smaller, tend to move faster than the larger white cells. As a result, red cells are confined to the central axial column, and leukocytes are pushed out toward the wall of the vessel, but the flow prevents the cells from attaching to the endothelium. As the blood flow slows early in inflammation (stasis), hemodynamic conditions change (wall shear stress decreases), and more white cells assume a peripheral position along the endothelial surface. This process of leukocyte redistribution is called margination. By moving close to the vessel wall, leukocytes are able to detect and react to changes in the endothelium. If the endothelial cells are activated by cytokines and other mediators produced locally, they express adhesion molecules to which the http://ebooksmedicine.net
Table 3.3 Properties of Neutrophils and Macrophages • Many tissue-resident macrophages: stem cells in yolk sac or fetal liver (early in development)
Life span in tissues 1–2 days Inflammatory macrophages: days or weeks Tissue-resident macrophages: years
Responses to activating stimuli Rapid, short-lived, mostly degranulation More prolonged, slower, often dependent on new gene and enzymatic activity transcription
Reactive oxygen species Rapidly induced by assembly of phagocyte Less prominent oxidase (respiratory burst)
Nitric oxide Low levels or none Induced following transcriptional activation of iNOS
Cytokine production Low levels or none Major functional activity, requires transcriptional activation of cytokine genes
NET formation Rapidly induced, by extrusion of nuclear No contents
Secretion of lysosomal enzymes Prominent Less
HSC, Hematopoietic stem cells; iNOS, inducible nitric oxide synthase; NET, neutrophil extracellular traps. This table lists the major differences between neutrophils and macrophages.The reactions summarized above are described in the text. Note that the two cell types share many features, such as phagocytosis, ability to migrate through blood vessels into tissues, and chemotaxis.
leukocytes attach loosely. These cells bind and detach and thus begin to tumble on the endothelial surface, a process called rolling. The cells finally come to rest at some point where they adhere firmly (resembling pebbles over which a stream runs without disturbing them).