Vascular endothelial growth factors synthesized by human lung mast cells exert angiogenic effects.
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 E(2) (PGE(2)) 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, PGE(2) and NECA enhanced VEGF-A release, and supernatants of PGE(2)- 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-A(165), VEGF-B(167), 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.


CONCLUSIONS
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.
Detoraki
Aikaterini
A
Department of Clinical Immunology and Allergy, Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy.
Staiano
Rosaria I
RI
Granata
Francescopaolo
F
Giannattasio
Giorgio
G
Prevete
Nella
N
de Paulis
Amato
A
Ribatti
Domenico
D
Genovese
Arturo
A
Triggiani
Massimo
M
Marone
Gianni
G
D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D002460:Cell Line; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology; D015232:Dinoprostone / Q000494:pharmacology; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010120:Oxytocics / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000096:biosynthesis*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis*; D042442:Vascular Endothelial Growth Factors / Q000819:agonists / Q000096:biosynthesis*; D014665:Vasodilator Agents / Q000494:pharmacology
D010120:Oxytocics; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014665:Vasodilator Agents; D019830:Adenosine-5'-(N-ethylcarboxamide); D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D015232:Dinoprostone