Migratory responses of PMN after intraperitoneal and intratracheal administration of lipopolysaccharide.

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.