[PDF][PDF] Role of complement, chemokines, & regulatory cytokines in acute lung injury

PA Ward - 1996 - deepblue.lib.umich.edu
PA Ward
1996deepblue.lib.umich.edu
Lung inflammatory injury triggered by intrapulmonary deposition of IgG immune complexes
has proven to be an important model for developing an understanding of the role of various
mediators in events that lead to tissue injury. A composite of events that are involved in
pathophysiological processes causing tissue injury following intrapulmonary deposition of
IgG immune complexes in rats is outlined in FIGURE 1. Initiation of this inflammatory
reaction is accomplished by the airway instillation of rabbit polyclonal IgG antibody to bovine …
Lung inflammatory injury triggered by intrapulmonary deposition of IgG immune complexes has proven to be an important model for developing an understanding of the role of various mediators in events that lead to tissue injury. A composite of events that are involved in pathophysiological processes causing tissue injury following intrapulmonary deposition of IgG immune complexes in rats is outlined in FIGURE 1. Initiation of this inflammatory reaction is accomplished by the airway instillation of rabbit polyclonal IgG antibody to bovine serum albumin (BSA), followed by the intravenous infusion of BSA. This results in deposition of immune complexes along the alveolar surfaces of lung. This event is, in turn, associated with activation of the complement system.’The composite result of these events is stimulation of pulmonary macrophages via a Mac-I-dependent (CDI Ib/CD18) pathway. 2 Stimulated pulmonary macrophages produce a series of cytokines, including the classical proinflammatory cytokines, tumor necrosis factor a (TNFa), and interleukin-1 (IL-11. j In addition, the chemokine macrophage inflammatory protein-la (MIP-la) has been demonstrated to be produced by these cells. Simultaneous production of IL-10 also OCCUI-S.~*~ TNFa and IL-1 probably play their most important role by causing upregulation of vascular (endothelial) adhesion molecules, including intercellular adhesion molecule-1 (ICAM-I) and E-selech6 The simultaneous production of MIP-la leads to another event, namely, autocrine stimulation of pulmonary macrophages, resulting in enhanced production of TNFm4 The upregulation of the vascular adhesion molecules in lung by TNFa and IL-1 leads to a sequence of adhesive interactions in which neutrophils first interact via their sialyl LewisX ligands with endothelial E-~ electin,’.~ which has been upregulated by TNFa and IL-I. In turn, adhesive interactions between neutrophil CDl la/CD18 (LFA-I) and endothelial ICAM-1 sets the stage for transmigration of ne~ trophils.~.~ Neutrophils that become adherent to endothelial cells via these various molecules may also become stimulated by endothelial cell expression of platelet activating factor (PAF) and interleukin-8 (IL-81, for which there are high-affinity receptors on the surfaces of neutrophils. Neutrophils then commence to their migration into the alveolar compartment in a manner that requires platelet endothelial cell adhesion molecule-I (PECAM-I). lo Transmigration is presumably under the regulation of chemotactic factors. The arrival of neutrophils into the alveolar compartment, together with the presence of activated macrophages, leads to injury of lung via the production by phagocytic cells of oxidants such as superoxide anion (O,.), H202 and nitric oxide (. NO),
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