Faculty Bibliography

Hemangioma is the most common soft-tissue tumor of infancy. Despite the frequency of these vascular tumors, the origin of hemangioma-endothelial cells is unknown. Circulating endothelial progenitor cells (EPCs) have recently been identified as vascular stem cells with the capacity to contribute to postnatal vascular development. We have attempted to determine whether circulating EPCs are increased in hemangioma patients and thereby provide insight into the role of EPCs in hemangioma growth. METHODS AND RESULTS: Peripheral blood mononuclear cells (PBMCs) were isolated from hemangioma patients undergoing surgical resection (N = 5) and from age-matched controls (N = 5) undergoing strabismus correction surgery. PBMCs were stained with fluorescent-labeled antibodies for AC133, CD34, and VEGFR2/KDR. Fluorescent-labeled isotype antibodies served as negative controls. Histologic sections of surgical specimens were stained with the specific hemangioma markers Glut1, CD32, and merosin, to confirm the diagnosis of common hemangioma of infancy. EPCs harvested from healthy adult volunteers were stained with Glut1, CD32, and merosin, to assess whether cultured EPCs express known hemangioma markers. Hemangioma patients had a 15-fold increase in the number of circulating CD34 AC133 dual-staining cells relative to controls (0.78+/-0.14% vs.0.052+/-0.017%, respectively). Similarly, the number of PBMCs that stained positively for both CD34 and KDR was also increased in hemangioma patients (0.49+/-0.074% vs. 0.19+/-0.041% in controls). Cultured EPCs stained positively for the known hemangioma markers Glut1, CD32, merosin. CONCLUSIONS: This is the first study to suggest a role for EPCs in the pathogenesis of hemangioma. Our results imply that increased levels of circulating EPCs may contribute to the formation of this vascular tumor

Recent studies have identified several coreceptors that are required for fusion and entry of Human Immunodeficiency Virus type 1 (HIV-1) into CD4+ cells. One of these receptors, CCR5, serves as a coreceptor for nonsyncytium inducing (NSI), macrophage-tropic strains of HIV-1, while another, fusin or CXCR-4, functions as a coreceptor for T cell line-adapted, syncytium-inducing (SI) strains. Using sequential primary isolates of HIV-1, we examined whether viruses using these coreceptors emerge in vivo and whether changes in coreceptor use are associated with disease progression. We found that isolates of HIV-1 from early in the course of infection predominantly used CCR5 for infection. However, in patients with disease progression, the virus expanded its coreceptor use to include CCR5, CCR3, CCR2b, and CXCR-4. Use of CXCR-4 as a coreceptor was only seen with primary viruses having an SI phenotype and was restricted by the env gene of the virus. The emergence of variants using this coreceptor was associated with a switch from NSI to SI phenotype, loss of sensitivity to chemokines, and decreasing CD4+ T cell counts. These results suggest that HIV-1 evolves during the course of infection to use an expanded range of coreceptors for infection, and that this adaptation is associated with progression to AIDS