Depletion of pulmonary intravascular macrophages partially inhibits lipopolysaccharide-induced lung inflammation in horses.
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.
Parbhakar
Om P
OP
Department of Veterinary Biomedical Sciences, University of Saskatchewan, 52 Campus Drive, Saskatoon, Saskatchewan S7N 5B4, Canada.
Duke
Tanya
T
Townsend
Hugh G G
HG
Singh
Baljit
B
D000818:Animals; D006734:Horse Diseases / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D006736:Horses; D007375:Interleukin-1 / Q000378:metabolism; D008070:Lipopolysaccharides; D008168:Lung / Q000473:pathology; D016676:Macrophages, Alveolar / Q000502:physiology*; D011014:Pneumonia / Q000276:immunology / Q000473:pathology / Q000662:veterinary*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha