Vascular endothelial growth factors synthesized by human lung mast cells exert angiogenic effects

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• 作者：Aikaterini Detoraki ; Rosaria I. Staiano ; Francescopaolo Granata ; Giorgio Giannattasio ; Nella Prevete ; Amato de Paulis ; Domenico Ribatti ; Arturo Genovese ; Massimo Triggiani ; Gianni Marone
• 关键词：Human mast cells ; vascular endothelial growth factors ; vascular endothelial growth factor receptors ; angiogenesis ; prostaglandin E₂ ; adenosine ; chemotaxis
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2009
• 出版时间：May 2009
• 年：2009
• 卷：123
• 期：5
• 页码：1142-1149.e5
• 全文大小：743 K

文摘

Background

Angiogenesis and lymphangiogenesis are critical for several allergic, inflammatory, and neoplastic disorders. Mast cells infiltrate the sites of inflammation and tumors.

Objective

We sought to characterize the expression and functions of vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) in human mast cells.

Methods

VEGF expression was evaluated by means of RT-PCR and Western blotting in primary human lung mast cells and in the mast cell lines LAD-2 and HMC-1. Angiogenic activity of mast cell supernatants was determined by using the chick embryo chorioallantoic membrane assay. VEGFR expression was assessed by means of RT-PCR and flow cytometry. Modified Boyden chambers were used for chemotaxis assay.

Results

Human mast cells express VEGF-A, VEGF-B, VEGF-C, and VEGF-D at both the mRNA and protein level. Prostaglandin E₂ (PGE₂) enhanced the expression of VEGFA, VEGFB, and VEGFC, whereas an adenosine analog (5′-[N-ethylcarboxamido] adenosine [NECA]) increased VEGFA, VEGFC, and VEGFD expression. In addition, PGE₂ and NECA enhanced VEGF-A release, and supernatants of PGE₂- and NECA-activated human lung mast cells induced angiogenic responses in the chorioallantoic membrane assay that were inhibited by an anti-VEGF-A antibody. Mast cells expressed mRNA for VEGFR1 and VEGFR2. These receptors were present on the mast cell surface. VEGF-A₁₆₅, VEGF-B₁₆₇, VEGF-C, VEGF-D, and placental growth factor 1 induced mast cell chemotaxis. These chemotactic effects were mediated by the activation of both VEGFR-1 and VEGFR-2.

Conclusion

Our data indicate that human mast cells are both a source and a target of angiogenic and lymphangiogenic factors and therefore might play a role in inflammatory and neoplastic angiogenesis through the expression of several forms of VEGFs and their receptors.