Acute respiratory distress syndrome (ARDS) is a serious form of acute lung injury (ALI), and has a high mortality of 30-50%. Understanding of ALI at molecular level may provide insights and lead to new therapies. PTX3 is a newly identified acute-phase protein, which can be induced from a variety of tissue cells on pro-inflammatory stimulations, such as LPS, IL1β and TNFα. In this study we sought to define the PTX3 expression patterns in multiple ALI models in rats and its relationship with the lung injury.
Rats were randomized to receive hemorrhagic (HS) or endotoxic shock (LPS) followed by resuscitation, or sham operation. Then the animals were subjected to either high (HV) or low (LV) volume ventilation for 4 hours. Blood gas, lung elastance, and wet/dry ratio were measured. PTX3, IL1β, and TNFα were assayed by quantitative real time PCR and ELISA. Distribution of PTX3 in the lung tissue was determined by immunohistochemistry.
After 4 hours of mechanical ventilation, the PTX3 expression in both mRNA and protein levels in the lung tissues were significantly enhanced by HS, or LPS, which is further increased by HV. In fact, HV alone also increased PTX3 expression significantly. In contrast, the serum level of PTX3 was found no obviously increase by HV and HS, but only slightly enhanced by LPS. Immunohistochemistry showed a profound positive staining of PTX3 on the epithelial layer of alveolar walls, indicating a major local response of PTX3 during ALI. The local PTX3 expression was well correlated with IL-1β and TNFα. Furthermore, the PTX3 expression was highly correlated with changes in wet/dry lung ratios, elastance, and PaO2, respectively (p < 0.0001).
PTX3 is an important inflammatory mediator whose expression can be increased by the inflammatory responses in the pathogenesis of ALI.
PTX3 might serve as a sensitive biomarker for local inflammatory responses during ALI.
Daisuke Okutani, None.