Cleavage Products of Complement Components Mediate Inflammation

The complement cascade is often viewed in terms of the final outcome of cell lysis, but various peptides generated during formation of the MAC play a decisive role in the development of an effective inflammatory response (see Table 13-3). The smaller fragments resulting from complement cleavage, C3a, C4a, and C5a, called anaphylatoxins, bind to receptors on mast cells and blood basophils and induce degranulation, with release of histamine and other pharmacologically active mediators. The anaphylatoxins also induce smooth-muscle contraction and increased vascular permeability. Activation of the complement system thus results in influxes of fluid that carries antibody and phagocytic cells to the site of antigen entry. The activities of these highly reactive anaphylatoxins are regulated by a serum protease called carboxypeptidase N, which cleaves an Arg residue from the C terminus of the molecules, yielding so-called des-Argforms. The des-Arg forms of C3a and C4a are completely inactive while that of C5a retains about 10% of its chemotactic activity and 1% of its ability to cause smooth muscle contraction.

C3a, C5a, and C5b67 can each induce monocytes and neutrophils to adhere to vascular endothelial cells, extravasate through the endothelial lining of the capillary, and migrate toward the site of complement activation in the tissues. C5a is most potent in mediating these processes, effective in picomolar quantities. The role of complement in leukocyte chemotaxis is discussed more fully in Chapter 15.

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Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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