Leukocyte Migration and Inflammation CHAPTER 15 VISUALIZING CONCEPTS BLOOD TISSUES Complement activation Histamine C c Prostaglandins VCAM-1 Leukotrienes f Mast cell Che S C3a C5a Chemokines Pselectin damage Leukotrienes Bradykinin Fibrin ICAM-1 FIGURE 15-12 Overview of the cells and mediators involved in induced by endothelial damage mediate vascular changes. Neu- a local acute inflammatory response. Tissue damage leads to the trophils generally are the first leukocytes to migrate into the tissue. formation of complement products that act as opsonins, anaphyla- followed by monocytes and lymphocytes. Only some of the interac toxins, and chemotactic agents. Bradykinin and fibrinopeptides tions involved in the extravasation of leukocytes are depicted ing to the swelling and redness in the area. when fluid exudes Within a few hours of the onset of these vascular changes. from the bloodstream, the kinin, clotting, and fibrinolytic sys- neutrophils adhere to the endothelial cells, and migrate tems are activated(see Figure 15-10). Many of the vascular out of the blood into the tissue spaces(Figure 15-12). These changes that occur early in a local response are due to the direct neutrophils phagocytose invading pathogens and release effects of plasma enzyme mediators such as bradykinin and fib- mediators that contribute to the inflammatory respons rinopeptides, which induce vasodilation and increased vascu- Among the mediators are the macrophage inflammatory lar permeability. Some of the vascular changes are due to the proteins(MIP-la and MIP-1B), chemokines that attract indirect effects of the complement anaphylatoxins(C3a, C4a, macrophages to the site of inflammation. Macrophages ar- and C5a), which induce local mast-cell degranulation with re- rive about 5-6 hours after an inflammatory response begins lease of histamine. Histamine is a potent mediator of inflam- These macrophages are activated cells that exhibit increased mation,causing vasodilation and smooth-muscle contraction. phagocytosis and increased release of mediators and cyto- The prostaglandins can also contribute to the vasodilation and kines that contribute to the inflammatory response increased vascular permeability associated with the acute in- Activated tissue macrophages secrete three cytokines (IL-1 IL-6, and TNF-a)that induce many of the localized anding to the swelling and redness in the area. When fluid exudes from the bloodstream, the kinin, clotting, and fibrinolytic sys￾tems are activated (see Figure 15-10). Many of the vascular changes that occur early in a local response are due to the direct effects of plasma enzyme mediators such as bradykinin and fib￾rinopeptides, which induce vasodilation and increased vascu￾lar permeability. Some of the vascular changes are due to the indirect effects of the complement anaphylatoxins (C3a, C4a, and C5a), which induce local mast-cell degranulation with re￾lease of histamine. Histamine is a potent mediator of inflam￾mation, causing vasodilation and smooth-muscle contraction. The prostaglandins can also contribute to the vasodilation and increased vascular permeability associated with the acute in￾flammatory response. Within a few hours of the onset of these vascular changes, neutrophils adhere to the endothelial cells, and migrate out of the blood into the tissue spaces (Figure 15-12). These neutrophils phagocytose invading pathogens and release mediators that contribute to the inflammatory response. Among the mediators are the macrophage inflammatory proteins (MIP-1 and MIP-1), chemokines that attract macrophages to the site of inflammation. Macrophages ar￾rive about 5–6 hours after an inflammatory response begins. These macrophages are activated cells that exhibit increased phagocytosis and increased release of mediators and cyto￾kines that contribute to the inflammatory response. Activated tissue macrophages secrete three cytokines (IL-1, IL-6, and TNF-) that induce many of the localized and Leukocyte Migration and Inflammation CHAPTER 15 351 VISUALIZING CONCEPTS Alternative or classical pathways Chemotaxis Chemotaxis Mast cell C3a, C5a C5b67 C3a C5a Histamine Prostaglandins Leukotrienes Prostaglandins Leukotrienes Fibrin Fibrinopeptides Bradykinin IL-1, IL-6, TNF-α Chemokines Complement activation Tissue damage Endothelial damage BLOOD TISSUES Bacteria Plasmin P-selectin PSGL-1 IL-8 VAL-4 VCAM-1 Monocyte LFA-1 ICAM-1 Lymphocyte Neutrophil Activated macrophage FIGURE 15-12 Overview of the cells and mediators involved in a local acute inflammatory response. Tissue damage leads to the formation of complement products that act as opsonins, anaphyla￾toxins, and chemotactic agents. Bradykinin and fibrinopeptides induced by endothelial damage mediate vascular changes. Neu￾trophils generally are the first leukocytes to migrate into the tissue, followed by monocytes and lymphocytes. Only some of the interac￾tions involved in the extravasation of leukocytes are depicted.