Abstract
The pathogenic mechanisms of lipopolysaccharide (LPS)-induced lung injury have not been classified. This study examined the physiological changes after endotoxin inhalation and related those to features of pulmonary inflammation in mice. Pulmonary mechanics, histopathology, and bronchoalveolar lavage fluid (BALF) from BALB/c mice were analysed at different occasions (3, 24, 48 and 72 h) after inhalation of saline or LPS from Escherichia coli (0.3 (L0.3) or 10 mg x mL(-1) (L10)). Mice were sedated, anaesthetized, and ventilated. After chest wall resection static (Est) and dynamic (Edyn) elastances, deltaE (Edyn-Est), resistive (deltaP1) and viscoelastic/inhomogeneous pressures (deltaP2), and deltaP1+deltaP2 (deltaPtot) were obtained by end-inflation occlusion method. Lungs were prepared for histopathology. In parallel groups, tumour necrosis factor (TNF)-alpha, neutrophils, and protein were evaluated in the BALF. L0.3 and L10 showed a time-dependent production of TNF-alpha preceding a massive neutrophil infiltration. In L10 BALF there was an increase in protein level at 24 and 48 h. Est and Edyn increased early in L0.3 (65%, 63%) and L10 (41%, 51%). In L10 deltaE, deltaP2, and deltaPtot showed a gradual rise. At 72 h all groups were similar. L0.3 showed an early increase in cellularity, which returned to normal at 72 h. L10 presented the same pattern with the cell count remaining elevated until 72 h. In conclusion, lipopolysaccharide inhalation led to elastic and viscoelastic pulmonary changes together with tumour necrosis factor-alpha production and neutrophil infiltration in mouse lung.
Highlights
L0.3 and L10 showed a time-dependent production of tumor necrosis factor (TNF)-a preceding a massive neutrophil infiltration
LPS mediates many of its effects through ligand-receptor interaction with a number of immune cells, which is followed by the release of a vast array of pro-inflammatory mediators that orchestrate the acute inflammatory response [2]
The activation of mononuclear phagocytes has a central role in this process, leading to the release of different cytokines, including tumor necrosis factor (TNF)a, considered as one of the most important mediators of endotoxin-induced tissue injury [1, 3, 4]
Summary
L0.3 and L10 showed a time-dependent production of TNF-a preceding a massive neutrophil infiltration. Lipopolysaccharide inhalation led to elastic and viscoelastic pulmonary changes together with tumour necrosis factor-a production and neutrophil infiltration in mouse lung. The activation of mononuclear phagocytes has a central role in this process, leading to the release of different cytokines, including tumor necrosis factor (TNF)a, considered as one of the most important mediators of endotoxin-induced tissue injury [1, 3, 4]. Different models of endotoxin-induced pulmonary injury have shown close correlations between neutrophil accumulation and tissue damage [10]. The inhalation model of endotoxin-induced injury triggers a pulmonary inflammatory cascade similar to that observed with haematogenic dissemination [2, 4, 5, 13, 15±17]. It mimics pulmonary inflammation secondary to natural exposure to LPS, being a model of direct pulmonary injury [4, 7, 18]
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