Monocyte chemoattractant protein-1 mRNA expression in hemangiomas and vascular malformations.

Hemangiomas are vascular tumors that appear at or shortly after birth and undergo a rapid growth before involuting. During the proliferative phase, hemangiomas are infiltrated by macrophages, cells that are capable of initiating angiogenesis. Vascular malformations grow slowly, commensurate with the child, and do not regress or become infiltrated by macrophages. We demonstrate by in situ hybridization increased monocyte chemoattractant protein-1 (MCP-1) mRNA expression during hemangioma and vascular malformation growth. We found markedly upregulated expression of MCP-1 mRNA in all proliferative hemangioma specimens, expressed by alpha-actin perivascular smooth muscle cells and interstitial HAM 56+ macrophages. In contrast, 9 of 10 clinically involuting hemangiomas displayed no expression of MCP-1 mRNA. We found no expression of MCP-1 mRNA in vascular malformations, which correlates with the minimal monocytic infiltration of these lesions. We also showed that dexamethasone and interferon-alpha downregulate MCP-1 mRNA in cultured human vascular smooth muscle cells. Glucocorticoids can be efficacious in 30-50% of cases when given in the proliferative phase of hemangioma growth, but have no beneficial effect on vascular malformations. Interferon-alpha has been used to dramatically induce regression of steroid-refractory hemangiomas. Both of these agents' beneficial action on proliferative hemangiomas may, in part, result from reduced MCP-1 production and reduced influx of angiogenic macrophages.