Abstract
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.
| Original language | English |
|---|---|
| Journal | Journal of Allergy and Clinical Immunology |
| Volume | 123 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 2009 |
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Keywords
- adenosine
- angiogenesis
- chemotaxis
- Human mast cells
- prostaglandin E
- vascular endothelial growth factor receptors
- vascular endothelial growth factors
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
Cite this
Vascular endothelial growth factors synthesized by human lung mast cells exert angiogenic effects. / Detoraki, Aikaterini; Staiano, Rosaria I.; Granata, Francescopaolo; Giannattasio, Giorgio; Prevete, Nella; de Paulis, Amato; Ribatti, Domenico; Genovese, Arturo; Triggiani, Massimo; Marone, Gianni.
In: Journal of Allergy and Clinical Immunology, Vol. 123, No. 5, 05.2009.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Vascular endothelial growth factors synthesized by human lung mast cells exert angiogenic effects
AU - Detoraki, Aikaterini
AU - Staiano, Rosaria I.
AU - Granata, Francescopaolo
AU - Giannattasio, Giorgio
AU - Prevete, Nella
AU - de Paulis, Amato
AU - Ribatti, Domenico
AU - Genovese, Arturo
AU - Triggiani, Massimo
AU - Marone, Gianni
PY - 2009/5
Y1 - 2009/5
N2 - 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.
AB - 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.
KW - adenosine
KW - angiogenesis
KW - chemotaxis
KW - Human mast cells
KW - prostaglandin E
KW - vascular endothelial growth factor receptors
KW - vascular endothelial growth factors
UR - http://www.scopus.com/inward/record.url?scp=67349091775&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67349091775&partnerID=8YFLogxK
U2 - 10.1016/j.jaci.2009.01.044
DO - 10.1016/j.jaci.2009.01.044
M3 - Article
C2 - 19275959
AN - SCOPUS:67349091775
VL - 123
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
SN - 0091-6749
IS - 5
ER -