Depletion of pulmonary intravascular macrophages partially inhibits lipopolysaccharide-induced lung inflammation in horses

Om P. Parbhakar; Tanya Duke; Hugh G.G. Townsend; Baljit Singh

doi:doi:10.1051/vetres:2005016

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Volume 36 / No 4 (July-August 2005)

Vet. Res., 36 4 (2005) 557-569

Abstract

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Issue		Vet. Res. Volume 36, Number 4, July-August 2005


Page(s)		557 - 569
DOI		https://doi.org/10.1051/vetres:2005016
How to cite this article		Vet. Res. (2005) 557-569

Vet. Res. 36 (2005) 557-569
DOI: 10.1051/vetres:2005016

Depletion of pulmonary intravascular macrophages partially inhibits lipopolysaccharide-induced lung inflammation in horses

Om P. Parbhakar^a, Tanya Duke^b, Hugh G.G. Townsend^c and Baljit Singh^{a, d}

^a Department of Veterinary Biomedical Sciences, University of Saskatchewan, 52 Campus Drive, Saskatoon, SK S7N 5B4, Canada
^b Small Animal Clinical Sciences, University of Saskatchewan, 52 Campus Drive, Saskatoon, SK S7N 5B4, Canada
^c Large Animal Clinical Sciences, University of Saskatchewan, 52 Campus Drive, Saskatoon, SK S7N 5B4, Canada
^d Immunology Research Group and Departments of the University of Saskatchewan, 52 Campus Drive, Saskatoon, SK S7N 5B4, Canada

(Received 16 April 2004; accepted 25 November 2004)

Abstract - 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-1 $\beta$ compared to control horses, which did not receive LPS (P < 0.05). However, GC-treated horses challenged with the LPS showed less IL-1 $\beta$ -positive cells (P < 0.05). Immuno-electron microscopy localized TNF- $\alpha$ and IL-1 $\beta$ in PIMs. These new data show that PIMs endocytose LPS and contain TNF- $\alpha$ and IL-1 $\beta$ and their depletion partially inhibits LPS-induced pulmonary inflammatory responses.

Key words: PIMs / TNF- $\alpha$ / IL-1 $\beta$ / gadolinium chloride / light and electron microscopic immunocytochemistry

Corresponding author: Baljit Singh baljit.singh@usask.ca

© INRA, EDP Sciences 2005