In:
European Journal of Immunology, Wiley, Vol. 34, No. 8 ( 2004-08), p. 2129-2137
Abstract:
Activated monocyte‐macrophages have been implicated in tumor angiogenesis via their capacity to produce many potent angiogenic factors. However, the mechanisms leading to production of these angiogenic factors in macrophages remain to be elucidated. In this study, we demonstrated by use of a mouse Matrigel implantation model that mouse peritoneal macrophages induce angiogenesis. mRNA expression and protein synthesis of macrophage‐derived crucial angiogenic factors such as IL‐1, TNF‐α, basic fibroblast growth factor, and vascular endothelial growth factor (VEGF) were blocked by platelet‐activating factor (PAF) receptor antagonists. It was also observed that inhibitors of NF‐κB blocked macrophage production of these angiogenic factors. Gene expression and protein synthesis of the angiogenic factors cited above were also inhibited in IκBα‐mutated macrophages. VEGF is the most potent angiogenic factor in macrophage‐induced angiogenesis. PAF antagonists or NF‐κB inhibitors also inhibit the capacity of conditioned medium from LPS‐stimulated human peripheral blood monocytes to induce sprouting of porcine pulmonary arterial endothelial cells. Thesedata indicate that PAF‐induced NF‐κB activation is a common upstream pathway leading to the production of crucial macrophage‐derived angiogenic factors. This will provide an important clue for a better understanding of mechanisms involved in tumor angiogenesis.
Type of Medium:
Online Resource
ISSN:
0014-2980
,
1521-4141
DOI:
10.1002/eji.200424957
Language:
English
Publisher:
Wiley
Publication Date:
2004
detail.hit.zdb_id:
120108-6
detail.hit.zdb_id:
1491907-2
