The acute inflammatory response is characterized by a rapid but relatively short-lived localized increase in blood flow, an increase in microvascular permeability and the sequential recruitment of different types of leukocytes. Acute inflammation may be followed by “chronic” inflammation and a superimposed 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 activated endothelial cells. In response to locally produced soluble and cell surface mediators, endothelial cells and rolling leukocytes sequentially express several sets of complementary adhesion molecules that include selectins, integrins, 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 along chemotactic gradients. Analogous, temporally regulated, soluble mediators and cellular adhesion molecules also orchestrate succeeding monocyte- and lymphocyte-rich chronic inflammatory responses. This paradigm is modulated by a vast network of surface-active and soluble inflammatory mediators. Recruited leukocytes and cells indigenous to the anatomic site of inflammation both play critical roles in host defense, resolution of inflammation and tissue repair.
Acronyms and Abbreviations:
ADAM, a disintegrin and metalloproteinase; BPI, bacterial permeability-increasing protein; CAP37, cationic antimicrobial protein; DARC, Duffy antigen receptor for chemokines; CD, cluster of differentiation; eNOS, endothelial nitric oxide synthase; HEV, high-endothelial venule; HPETE, hydroperoxyeicosatetraenoic acid; ICAM, intercellular adhesion molecule; IFN, interferon; Ig, immunoglobulin; IL, interleukin; iNOS, inducible nitric oxide synthase; LT, leukotriene; LTB4/C4/D4/E4, leukotriene B4/C4/D4/E4; MadCAM, mucosal addressin cell adhesion molecule; MASP, mannan-binding lectin-associated serine protease; MBL, mannan-binding lectin; NADPH, nicotinamide adenine dinucleotide phosphate (reduced); NO, nitric oxide; PAF, platelet-activating factor; PARs, proteinase-activated receptors; PNAd, peripheral node addressin; PSGL-1, P-selectin glycoprotein ligand-1; RGD, arginine-glycine-aspartic acid peptide sequence; TACE, tumor necrosis factor-α converting enzyme; 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 at least 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, German pathologist Julius Cohnheim concluded that the inflammatory response is fundamentally a vascular phenomenon. Phagocytosis was described late in the 19th century by Elie Metchnikoff and his colleagues at the Pasteur Institute. 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 ...