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The Utilization of Oropharyngeal Intratracheal PAMP Administration and Bronchoalveolar Lavage to Evaluate the Host Immune Response in Mice
Published on: April 2, 2014
Migratory responses of PMN after intraperitoneal and intratracheal administration of lipopolysaccharide
1Regional Environment Division, National Institute for Environmental Studies, Ibaraki, Japan. seishiro@nies.go.p
Abstract:
The present study was undertaken primarily to investigate accumulation of polymorphonuclear leukocytes (PMN) within the lung vasculature after intraperitoneal injection of lipopolysaccharide (LPS) and migratory responses of those intravascular PMN to intratracheally instilled LPS in mice. Intraperitoneally injected LPS was absorbed into the blood rapidly, and the concentration of circulating LPS peaked at 1 h postinjection. Tumor necrosis factor concentration in blood began to increase at 0.5 h and also peaked at 1 h postinjection. The number of lung vascular-associated PMN was increased 7.5-fold at 0.5 h post-intraperitoneal injection. However, neither diapedesis of PMN nor injury was observed in the lung, while mixed cell infiltration was observed in the liver. Although intraperitoneally injected LPS caused a significant PMN accumulation within the lung vasculature, pre-intraperitoneal injection of LPS dramatically and dose dependently abolished both intratracheal LPS-inducible PMN infiltration and apparent plasma protein leakage into the alveolar space. On the other hand, pre-intratracheal instillation of LPS enhanced rather than reduced intraperitoneal LPS-inducible PMN infiltration into the peritoneal cavity. In rats, a sublethal dose of intraperitoneally injected LPS caused a modest increase in alveolar PMN and yet reduced intratracheal LPS-inducible robust transpulmonary PMN infiltration. Although mechanisms of different migratory responses of the lung vasculature-associated PMN are unknown, the inhibitory effects of intraperitoneally injected LPS on transpulmonary PMN infiltration may be applicable to treatments for septic lung diseases.
Insights
Intraperitoneal lipopolysaccharide (LPS) injection causes polymorphonuclear leukocytes (PMN) to accumulate in lung blood vessels. Pre-treatment with LPS inhibits PMN lung infiltration, suggesting potential treatments for septic lung diseases.
Area of Science:
- Immunology
- Pulmonary Medicine
- Pharmacology
Background:
- Lipopolysaccharide (LPS) is a potent endotoxin that triggers inflammatory responses.
- Polymorphonuclear leukocytes (PMN) play a critical role in host defense and inflammation.
- Understanding PMN migration is crucial for treating inflammatory lung diseases.
Purpose of the Study:
- To investigate PMN accumulation in lung vasculature after intraperitoneal LPS injection.
- To examine the migratory response of intravascular PMN to intratracheal LPS.
- To explore the potential therapeutic implications of LPS administration on lung inflammation.
Main Methods:
- Mice and rats were administered LPS via intraperitoneal injection and/or intratracheal instillation.
- Circulating LPS and tumor necrosis factor (TNF) levels were measured.
- PMN accumulation in lung vasculature and infiltration into alveolar spaces were assessed.
- Plasma protein leakage into the alveolar space was quantified.
Main Results:
- Intraperitoneal LPS rapidly increased circulating LPS and TNF levels, peaking at 1 hour.
- A significant 7.5-fold increase in lung vascular-associated PMN was observed 0.5 hours post-intraperitoneal LPS.
- Pre-treatment with intraperitoneal LPS dose-dependently inhibited both intratracheal LPS-induced PMN infiltration and plasma leakage into the alveolar space.
- Intratracheal LPS enhanced peritoneal PMN infiltration, while intraperitoneal LPS reduced transpulmonary PMN infiltration in rats.
Conclusions:
- Intraperitoneal LPS induces PMN accumulation in lung vasculature but inhibits subsequent transpulmonary PMN migration.
- Prior systemic LPS exposure can modulate inflammatory responses in the lungs.
- The inhibitory effect of intraperitoneal LPS on transpulmonary PMN infiltration may offer a novel therapeutic strategy for septic lung diseases.
