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Granger DN, Senchenkova E. Inflammation and the Microcirculation. San Rafael (CA): Morgan & Claypool Life Sciences; 2010.

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Inflammation and the Microcirculation.

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Chapter 2Historical Perspectives

The history of inflammation is long and colorful, with descriptions of this process dating back to the ancient Egyptian and Greek cultures. Terms, like edema, which are still used to describe inflammation, were introduced by Hippocrates in the 5th century BC. He also regarded inflammation as an early component of the healing process after tissue injury. Aulus Celsus, a Roman writer who lived between 30 BC and 45 AD, described the main four signs of inflammation as redness, warmth, swelling, and pain. We now appreciate that the first three signs are likely attributable to responses of the microvasculature to inflammation. Galen, the physician and surgeon of Roman emperor Marcus Aurelius, is often credited with introducing a fifth sign of inflammation, i.e., loss of function in the affected tissue. Galen also attributed a role for the percolation of blood, which he introduced as one of the four vital humors, in the inflammatory process. While these early concepts about inflammation were largely derived from intuition rather than careful scientific investigation, the controversial observations described by the ancient cultures provided the framework for critical experimentation in the later centuries [611].

The invention of the compound microscope by Janssen in the 16th century and the subsequent improvement of its optical resolution by Leeuwenhoek gave rise to the early descriptions of the microcirculation and its responses to inflammation. Eighteenth-century applications of the microscope lead to descriptions of blood flow changes in inflamed tissue and the proposal by Gaubius that inflammation can promote the “disposition to coagulation.” In 1794, John Hunter first used the term angiogenesis to describe the development of growing blood vessels in healing wounds. Dutrochet (1824) provided the first description of the “sticking” and emigration of white cells (described as “vesicular globules”) in blood vessels during acute inflammation, while the first explicit description of leukocyte rolling is attributed to Wagner in 1839. Cohnheim’s (1867) classical descriptions of vascular events in thin, transparent tissues in vivo lead him to postulate that “molecular alteration in the vessel walls” underlies the sticking of leukocytes in inflamed microvessels, while their subsequent emigration was attributed to mechanical filtration. Metchnikoff (1893), on the other hand, assigned a more important role for the leukocyte in the emigration process, stating that “the migration is effected by the amoeboid power of the leukocytes.” Cohnheim’s observations also lead him to speculate that augmented “porousness” of the vessel wall explain the enhanced fluid and protein transudation in inflamed tissue [8,9,1821].

The 20th century was marked by rapid advancements in understanding the nature and underlying mechanisms of the microvascular responses to inflammation. The development of new in vivo models of inflammation, methods to capture and store images of the microcirculation, and the application of mathematical and engineering approaches to quantify variables such as leukocyte adhesion, vasomotor function, and vascular permeability allowed the field to move forward at a greatly accelerated pace. This period also brought new chemical methods that enabled the discovery of different inflammatory mediators and coagulation factors. With the advent of the electron microscope came the first descriptions of the fine structure of the endothelial cell and other components of the vessel wall. The multifunctional nature of ECs and their critical role in the inflammatory response was born from the explosion of endothelial cell research that began in the 1970s. An outgrowth of this new focus on ECs was the successful effort to isolate and culture ECs from human umbilical veins, which formed the basis for development of in vitro models to study molecular mechanisms underlying endothelium-dependent inflammatory processes such as leukocyte recruitment, thrombosis, increased vascular permeability, and angiogenesis [11,2224].

In recent years, important additions to the armamentarium of inflammation researchers have come from the fields of molecular biology and immunology. The development of gene-targeted knock-out mice for different inflammatory molecules, such as cytokines, chemokines, and their receptors, as well as leukocyte and endothelial cell adhesion molecules have proven to be immensely useful in the dissection of molecular mechanisms of inflammation in vivo. Immunological approaches (e.g., blocking antibodies, bone marrow chimeras) developed for the mouse, with its exhaustively characterized immune system, have also proven to be powerful tools for the study of inflammation. The large impact of these developments on inflammation research holds promise for further advancements that can result from the continued rapid development of novel technologies and experimental approaches in different areas of biomedical research [8,11,12].

Copyright © 2010 by Morgan & Claypool Life Sciences.
Bookshelf ID: NBK53379
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