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Provocation of experimental aortic inflammation and dilatation by inflammatory mediators and Chlamydia pneumoniae
J Tambiah1, I J Franklin, N Trendell-Smith
1Department of Vascular Surgery, Imperial College at Charing Cross, London, UK.
Background:
The macrophage appears to have a key role in the inflammation and proteolysis associated with the growth and development of abdominal aortic aneurysms. The role of inflammatory mediators and Chlamydia pneumoniae in stimulating the influx of macrophages and dilatation of the abdominal aorta was investigated in an experimental model.
Methods:
Periaortic application of calcium chloride solution (and monocyte chemoattractant protein (MCP) 1, a cocktail of cytokines or C. pneumoniae) to the abdominal aorta of New Zealand White rabbits was performed at laparotomy. Some animals were fed a cholesterol-rich diet. The diameter of the aorta was measured by ultrasonography and after perfusion fixation, 3 weeks after laparotomy. Aortic sections were stained with RAM-11 to identify macrophages for counting. The presence of C. pneumoniae DNA was confirmed using the polymerase chain reaction.
Results:
Aortic macrophage influx in response to MCP-1, thioglycollate or C. pneumoniae was more than doubled in the cholesterol-fed animals. In response to human recombinant MCP-1 (1 microg) the mean(s.d.) macrophage count increased from 79(19) to 340(215) per unit area (P < 0.02). Even in cholesterol-fed animals, application of MCP-1 (recombinant human or rabbit form) was not associated with aortic dilatation. Application of thioglycollate 0.1 mol/l, or live or formalin-inactivated C. pneumoniae (0.5 x 108 organisms), was associated with a similar increase in macrophages to that caused by MCP-1 and a significant (approximately twofold) increase in aortic diameter after 3 weeks.
Conclusion:
Macrophage influx into rabbit abdominal aorta, without macrophage activation, is insufficient to cause experimental aortic dilatation. C. pneumoniae antigens appeared to stimulate aortic dilatation, probably by specific activation of macrophages.
Insights
Macrophage influx alone does not cause abdominal aortic aneurysms. However, Chlamydia pneumoniae antigens may stimulate aortic dilatation by activating macrophages in this experimental model.
Area of Science:
- Vascular Biology
- Immunology
- Microbiology
Background:
- Macrophages play a crucial role in abdominal aortic aneurysm (AAA) development through inflammation and proteolysis.
- Investigating inflammatory mediators and Chlamydia pneumoniae's role in AAA pathogenesis is essential.
Purpose of the Study:
- To investigate the role of inflammatory mediators and Chlamydia pneumoniae in stimulating macrophage influx and aortic dilatation in an experimental AAA model.
- To determine if macrophage influx alone is sufficient to cause aortic dilatation.
Main Methods:
- Rabbits underwent laparotomy with periaortic application of calcium chloride, monocyte chemoattractant protein-1 (MCP-1), cytokines, or C. pneumoniae.
- Some rabbits were fed a cholesterol-rich diet, and aortic diameter was measured via ultrasonography.
- Aortic sections were stained for macrophages (RAM-11), and C. pneumoniae DNA was detected using PCR.
Main Results:
- Cholesterol-fed rabbits showed doubled macrophage influx in response to MCP-1, thioglycollate, or C. pneumoniae.
- MCP-1 administration increased macrophage counts significantly but did not cause aortic dilatation.
- Thioglycollate or C. pneumoniae administration led to increased macrophages and a significant twofold increase in aortic diameter.
Conclusions:
- Macrophage influx into the abdominal aorta, without activation, is insufficient to induce experimental aortic dilatation.
- Chlamydia pneumoniae antigens appear to stimulate aortic dilatation, likely through specific macrophage activation.