Macrophages interstitial

One intensively investigated feature of the inflammatory process in COPD is the release of proteases from neutrophils and monocytic cells that destroy elastin and other components of the interstitial matrix (Table 1). The best studied protease is neutrophil elastase. Independent of its elastolytic activity, neutrophil elastase is a potent secretagogue. More recently matrix metalloproteases (MMP) have received increasing attention, in particular MMP 12 (macrophages elastase). To which extent and how exactly these proteases become activated is not clear at present. 

Inflammation. Figure 1 Sequence of events in the recruitment of leukocytes in postcapillary venules adjacent to injured tissue. At the site of lesion, diverse reactive substances stimulate the endothelium to produce inflammatory cytokines, chemoattractants and other inflammatory mediators. The cytokine-activated endothelium expresses adhesion molecules that lead to the low affinity interactions between leukocytes and endothelium, which is mediated by selectins and described as rolling. Subsequently integrins mediate the firm adhesion of leukocytes, which allows emigration of the cells from venules into the interstitial compartment. Activated mast cells, PMNs and macrophages secrete cytokines (TNFa), lipid mediators (LTB4) and other inflammatory players (histamine, NO). 

Wizemann, T.M. and Laskin, D.L. Enhanced phagocytosis, chemotaxis, and production of reactive oxygen intermediates by interstitial lung macrophages following acute endo-toxemia, Am. J. Respir. Cell Mol. Biol., 11, 358, 1994. 

A number of studies of the toxicity of zinc oxide/hexachloroethane smoke have been conducted (Brown et al. 1990 Karlsson et al. 1986 Marrs et al. 1983). These studies demonstrate that smoke exposure results in pulmonary inflammation and irritation. When male Porton Wistar rats were exposed to hexachloroethane/zinc oxide smoke for 60 minutes, the lungs showed pulmonary edema, alveolitis, and areas of macrophage infiltration 3 days later. At 14 days, there was interstitial fibrosis and macrophage infiltration. At 28 days, increased fibrosis and macrophage infiltration were noted. However, these same symptoms occurred when the animals inhaled zinc chloride there was no apparent synergism between the zinc chloride and residual hexachloroethane (Brown et al. 1990 Richard et al. 1989). This is consistent with the fact that smoke contains little hexachloroethane and the observation that acute exposure to 260 ppm hexachloroethane had no effects on the lungs of rats (Weeks et al. 1979). 

Numerous studies in animals have investigated the respiratory effects of nickel exposure. Intermittent exposure (6 hours/day, 5 days/week) of rats and mice for 16 days or 13 weeks resulted in chronic active inflammation in the lungs, fibrosis, macrophage hyperplasia, interstitial infiltrates, and increased lung weight following exposure to 0.06 mg nickel/m as nickel sulfate, 0.11 mg nickelM as nickel subsulfide, and 0.4 mg nickel/m as nickel oxide (Benson et al. 1987, 1988, 1989 Durmick et al. 

Respiratory effects in animals after inhalation exposure to nickel were similar to those observed in humans. The effects included increased lung weights, emphysema, chronic inflammation, fibrosis, macrophage hyperplasia, interstitial infiltrates, and atrophy of the olfactory epithelium (Benson et al. 1989 Dunnick et al. 1989 NTP 1996a, 1996b, 1996c Ottolenghi et al. 1974). Respiratory effects in animals were observed after inhalation exposure to both soluble and less-soluble nickel compounds. 

Extracellular antigens are detected by APCs, such as lymphocytes, macrophages, and dendritic cells in interstitial fluid and blood. These detect the hapten and engulf the whole antigenic complex. Then, when inside the APC, the complex is partly dismantled and peptides attached to proteins similar to immunoglobulins, known as MHC II. The modified peptide-hapten complex is moved to the surface of the APC and presented as a complex with MHC to T-helper cells (CD4+), which activates and instructs the APC to make antibodies to the hapten and also B cells (memory cells with "memory" of the hapten) to proliferate. These events lead to types I to III responses. 

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