Provocation of experimental aortic inflammation and dilatation by inflammatory mediators and Chlamydia pneumoniae

Abstract

Abstract 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 µg) 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 × 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.