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Increased expression of vascular cell adhesion molecule-1 by the aortic endothelium of rabbits with Pasteurella
M Richardson1, A Fletch, K Delaney
1Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Abstract:
Vascular cell adhesion molecule-1 (VCAM-1) is expressed by endothelial cells in a variety of inflammatory conditions in experimental animals and humans. It is increased in rabbit endothelium after the intravenous administration of endotoxin, after cholesterol feeding, in regeneration after injury, and in alloxan-induced diabetes mellitus. The effect of a respiratory tract infection with Pasteurella multocida, a common laboratory pathogen in rabbits, on VCAM-1 expression by aortic endothelial cells and on the endothelial ultrastructure was examined in specific-pathogen-free (SPF) New Zealand White rabbits infected by the instillation of a suspension of live organisms into the nose and in conventionally raised rabbits with naturally acquired P. multocida infection. Age-matched SPF rabbits maintained in a disease-free environment were controls. Rabbits were euthanized 50 days after infection, the aorta was excised, and the endothelial cells expressing VCAM-1 were identified by immunohistochemistry. Perfusion-fixed aortas from infected and SPF rabbits were prepared for examination by electron microscopy. All infected animals had pneumonitis and leukocytosis. In SPF rabbits the total leukocyte count was highest at postinfection day 25. There was a significant (P < 0.05) increase in the number of VCAM-1-positive aortic endothelial cells in infected SPF rabbits (34 +/- 4/10(4) endothelial cells; n = 5) and rabbits with naturally acquired infection (57 +/- 14/10(4) endothelial cells; n = 5) compared with control animals (12 +/- 3 per 10(4) endothelial cells; n = 4). The endothelium of infected rabbits had morphologic alterations consistent with injury. Thus infection at remote sites can activate arterial endothelium and induce the expression of VCAM-1.
Insights
Respiratory tract infection with Pasteurella multocida significantly increases vascular cell adhesion molecule-1 (VCAM-1) in aortic endothelial cells. This remote infection activates arterial endothelium and alters its ultrastructure, indicating a link between infection and vascular inflammation.
Area of Science:
- Vascular biology
- Immunology
- Pathology
Background:
- Vascular cell adhesion molecule-1 (VCAM-1) is upregulated in endothelial cells during various inflammatory conditions.
- Previous studies show increased VCAM-1 in rabbits due to endotoxin, cholesterol feeding, injury, and diabetes.
Purpose of the Study:
- To investigate the effect of Pasteurella multocida respiratory infection on VCAM-1 expression in aortic endothelial cells.
- To examine the impact of infection on endothelial ultrastructure in rabbits.
Main Methods:
- Specific-pathogen-free (SPF) and conventionally raised rabbits were infected with P. multocida.
- Aortic endothelial cells were analyzed for VCAM-1 expression using immunohistochemistry.
- Endothelial ultrastructure was examined via electron microscopy.
Main Results:
- Infected rabbits exhibited pneumonitis and leukocytosis.
- A significant increase in VCAM-1-positive aortic endothelial cells was observed in infected SPF rabbits and those with natural infection compared to controls.
- Morphological alterations consistent with endothelial injury were noted in infected rabbits.
Conclusions:
- Respiratory tract infections can activate arterial endothelium at remote sites.
- P. multocida infection induces VCAM-1 expression in aortic endothelium.
- Infection leads to endothelial injury and VCAM-1 upregulation, highlighting a connection between distant infections and vascular inflammation.