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Background: Granulocyte macrophage colony-stimulating factor (GM-CSF) deficiency affects the production and fiber assembly/organization of the vascular collagenous matrix; structural alterations to the elastic system were observed. The present study elaborates the effect of GM-CSF deficiency on the vascular elastin system. Methods and Results: Histological examination of the aorta of GM-CSF-deficient mice revealed structurally altered elastic fibers. The elastic fiber area was significantly enhanced, whereas the remaining medial area was not affected. Aortic size was significantly increased. Reverse transcription polymerase chain reaction demonstrated decreased expression levels of tropoelastin, lysyl oxidase and bone morphogenetic protein 1 (BMP-1). Cell culture studies on vascular smooth muscle cells showed that after clearance of GM-CSF with GM-CSF antibodies, the tropoelastin mRNA expression was markedly reduced. Concomitantly, lysyl oxidase and BMP-1 mRNA levels were decreased. Treatment with GM-CSF stimulated the expression of these mRNAs. Conclusions: Our studies demonstrate that disorganization of elastic lamellae as induced by GM-CSF deficiency is associated with adaptive vascular remodeling. The decreased tropoelastin expression observed is associated with elastic fiber hypertrophy. This paradox effect may be explained by decreased expression levels of lysyl oxidase and BMP-1, both mediating cross-linkage and thus assembly and organization of elastic fibers. From our data, we conclude that GM-CSF is a prerequisite for the maintenance of structural integrity of the vessel wall.

The ultrastructural changes in the liver cells of male Wistar rats induced by oral and subcutaneous application of o-phenylphenol were studied electron microscopically using the thin section and freeze-fracture technique. The rats were given the o-phenylphenol once at a dose of 2,500 mg/kg b.w. and were sacrificed 60 h after treatment. In the orally treated animals, alterations in the nuclei and nucleoli of the hepatocytes were the most prominent alterations. Furthermore, an increase in smooth endoplasmic reticulum, lysosomes and microbodies were found. After the subcutaneous injection of o-phenylphenol enlargements of the bile canaliculi, intercellular space and pathological alterations in the mitochondria were seen. A proliferation of the smooth endoplasmic reticulum, an increase of microbodies and a decrease in the rough endoplasmic reticulum could be found. Both groups showed an increase in small intracellular fat droplets in the hepatocytes. In general, the effects of the subcutaneous application on the liver were more pronounced than the effects of the oral application. Freeze-fracture replicas exhibited a disorganization of the zonulae occludentes and an apparent increase in the number and size of gap junctions. These alterations were interpreted as an attempt of the liver cells to counteract the intracanalicular pressure and to increase the mechanical stability of the liver tissue.