Parbhakar Om P, Duke Tanya, Townsend Hugh G G, Singh Baljit
Department of Veterinary Biomedical Sciences, University of Saskatchewan, 52 Campus Drive, Saskatoon, Saskatchewan S7N 5B4, Canada.
Vet Res. 2005 Jul-Aug;36(4):557-69. doi: 10.1051/vetres:2005016.
Horses are unique in their extreme sensitivity to endotoxin-induced cardio-pulmonary shock and mortality. The mechanisms behind increased sensitivity of the horse to endotoxin remain unknown. Pulmonary intravascular macrophages (PIMs) are pro-inflammatory cells occurring in horses. Because the functions of equine PIMs in endotoxemia remain unknown, we studied the role played by equine PIMs in endotoxin-induced pulmonary pathophysiology. We achieved this by using a recently developed protocol to deplete PIMs in order to compare lipopolysaccharide (LPS)-induced pulmonary responses in horses with or without PIMs. Horses treated with gadolinium chloride (GC; 10 mg/kg intravenous) to deplete PIMs or endotoxin-free saline (n = 4) were injected with Escherichia coli LPS (E. coli LPS; 50 ng/kg intravenously) 48 h after GC or saline. Control horses (n = 5) received two injections of endotoxin-free saline at 48 h intervals. All the horses were euthanized 2 h after LPS or saline challenge. Immunohistology for the PIMs showed their reduced numbers in GC-treated horses. The LPS treatment of normal and GC-treated horses increased diastolic and systolic pulmonary arterial pressures at 30 min compared to the saline-treated horses (P < 0.05). However, horses pre-treated with GC did not have an LPS-induced increase in mean pulmonary arterial pressure compared to the LPS-treated horses (P < 0.05). Light and electron microscopic immunocytochemistry detected extensive labeling for LPS in PIMs of LPS-treated horses. Both the LPS-treated groups had more alveolar septal cells positive for TNF-alpha and IL-1beta compared to control horses, which did not receive LPS (P < 0.05). However, GC-treated horses challenged with the LPS showed less IL-1beta-positive cells (P < 0.05). Immuno-electron microscopy localized TNF-alpha and IL-1beta in PIMs. These new data show that PIMs endocytose LPS and contain TNF-alpha and IL-1beta and their depletion partially inhibits LPS-induced pulmonary inflammatory responses.
马对内毒素诱导的心肺休克和死亡率极度敏感，这一点十分独特。马对内毒素敏感性增加背后的机制尚不清楚。肺血管内巨噬细胞（PIMs）是马体内存在的促炎细胞。由于马的PIMs在内毒素血症中的功能尚不清楚，我们研究了马的PIMs在内毒素诱导的肺部病理生理学中所起的作用。我们通过使用最近开发的方案来消耗PIMs，以便比较有或没有PIMs的马在脂多糖（LPS）诱导下的肺部反应。用氯化钆（GC；10mg/kg静脉注射）处理以消耗PIMs的马或无内毒素生理盐水（n = 4）在GC或生理盐水处理48小时后静脉注射大肠杆菌LPS（大肠杆菌LPS；50ng/kg）。对照马（n = 5）每隔48小时接受两次无内毒素生理盐水注射。在LPS或生理盐水攻击2小时后，所有马均实施安乐死。对PIMs的免疫组织学检查显示，在接受GC处理的马中其数量减少。与接受生理盐水处理的马相比，正常马和接受GC处理的马在LPS处理后30分钟时舒张期和收缩期肺动脉压升高（P < 0.05）。然而，与接受LPS处理的马相比，预先用GC处理的马在LPS诱导下平均肺动脉压没有升高（P < 0.05）。光镜和电镜免疫细胞化学检测到在接受LPS处理的马的PIMs中有大量LPS标记。与未接受LPS的对照马相比，两个接受LPS处理的组中TNF-α和IL-1β阳性的肺泡隔细胞更多（P < 0.05）。然而，接受GC处理并用LPS攻击的马中IL-1β阳性细胞较少（P < 0.05）。免疫电子显微镜将TNF-α和IL-1β定位在PIMs中。这些新数据表明，PIMs内吞LPS并含有TNF-α和IL-1β，其消耗可部分抑制LPS诱导的肺部炎症反应。
