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The inflammatory response is characterized by a rapid but relatively short-lived increase in local blood flow, an increase in microvascular permeability, and the sequential recruitment of different types of leukocytes. Superimposed is a series of reparative processes (e.g., angiogenesis, production of extracellular matrix, parenchymal regeneration, and scar formation). The early hemodynamic changes at a site of inflammation establish low shear conditions that enable marginated leukocytes to engage in low-affinity selectin-mediated rolling interactions with endothelial cells. In response to locally produced soluble and cell surface mediators, endothelial cells and rolling leukocytes become activated and sequentially express sets of complementary adhesion molecules that include β2 integrins, selectins, and members of the immunoglobulin superfamily. Leukocyte and endothelial cell adhesion molecules mediate the high-affinity adhesive interactions necessary for leukocyte emigration from the vascular space and along chemotactic gradients. Analogous, temporally regulated, soluble mediators and cellular adhesion molecules also orchestrate succeeding monocyte- and lymphocyte-rich chronic inflammatory responses. This basic paradigm is modulated by numerous surface-active and soluble inflammatory mediators. Recruited leukocytes and cells indigenous to the anatomic site of inflammation both play critical roles in host defense and tissue repair.

Acronyms and Abbreviations

Acronyms and abbreviations that appear in this chapter include: BPI, bactericidal/permeability-increasing protein; CAP37, cationic antimicrobial protein; CD, cluster of differentiation; eNOS, endothelial nitric oxide synthase; HEV, high endothelial venules; HPETE, hydroperoxyeicosatetraenoic acid; ICAM, intercellular adhesion molecule; Ig, immunoglobulin; IL, interleukin; iNOS, inducible nitric oxide synthase; LT, leukotriene; LTB4 / C4 / D4 / E4, leukotriene B4 / C4 / D4 / E4; MASP, mannan-binding lectin-associated serine protease; MBL, mannan-binding lectin; NADPH, nicotinamide adenine dinucleotide phosphate (reduced); nNOS, neuronal nitric oxide synthase; NO, nitric oxide; NOS, nitric oxide synthase; PAF, platelet-activating factor; PSGL-1, P-selectin glycoprotein ligand-1; RGD, arginine-glycine-aspartic acid peptide sequence; TNF, tumor necrosis factor; VCAM, vascular cell adhesion molecule; VLA, very-late antigen.

The sentinel clinical features of acute inflammation—rubor, calor, tumor, and dolor—have been recognized for 5000 years.1 Dr. John Hunter, the renowned late-18th-century Scottish surgeon, observed that the inflammatory response is not a disease per se but rather a nonspecific and salutary response to a variety of insults. Through his microscopic examinations of transparent vital membrane preparations, Julius Cohnheim concluded that the inflammatory response is fundamentally a vascular phenomenon. Phagocytosis was described in the late 19th century by Eli Metchnikoff and his colleagues. Morphologic studies, using both live animals and fixed histologic preparations, transformed our understanding of inflammation and led to the currently held concepts of inflammation-associated hemodynamic alterations, “acute” inflammation, and “chronic” inflammation.1,2 During the past 5 decades, the modern techniques of biochemistry, tissue culture, monoclonal antibody production, recombinant DNA technology, and the genetic manipulation of isolated cells and whole animals have enabled a more detailed understanding of the cellular and molecular mechanisms that characterize the inflammatory response. These studies, in concert with “experiments of nature” such as chronic granulomatous disease ...

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