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Expression and Functions of the Vascular Endothelial Growth Factors and Their Receptors in Human Basophils¹

Amato de Paulis^*, Nella Prevete^*, Isabella Fiorentino^*, Francesca Wanda Rossi^*, Stefania Staibano, Nunzia Montuori, Pia Ragno, Amelia Longobardi^*, Bianca Liccardo^*, Arturo Genovese^*, Domenico Ribatti, Andrew F. Walls^¶ and Gianni Marone^2,*

^* Divisione di Immunologia Clinica ed Allergologia e Centro Interdipartimentale di Ricerca di Scienze Immunologiche di Base e Cliniche, Dipartimento di Scienze Biomorfologiche e Funzionali–Sezione di Anatomia Patologica, and Istituto di Endocrinologia ed Oncologia Sperimentale, Università di Napoli Federico II, Naples, Italy; Dipartimento di Anatomia Umana ed Istologia, Università di Bari, Bari, Italy; and ^¶ Immunopharmacology Group, Southampton General Hospital, Southampton, United Kingdom

Angiogenesis is a multistep complex phenomenon critical for several inflammatory and neoplastic disorders. Basophils, normally confined to peripheral blood, can infiltrate the sites of chronic inflammation. In an attempt to obtain insights into the mechanism(s) underlying human basophil chemotaxis and its role in inflammation, we have characterized the expression and function of vascular endothelial growth factors (VEGFs) and their receptors in these cells. Basophils express mRNA for three isoforms of VEGF-A (121, 165, and 189) and two isoforms of VEGF-B (167 and 186). Peripheral blood and basophils in nasal polyps contain VEGF-A localized in secretory granules. The concentration of VEGF-A in basophils was 144.4 ± 10.8 pg/10⁶ cells. Immunologic activation of basophils induced the release of VEGF-A. VEGF-A (10–500 ng/ml) induced basophil chemotaxis. Supernatants of activated basophils induced an angiogenic response in the chick embryo chorioallantoic membrane that was inhibited by an anti-VEGF-A Ab. The tyrosine kinase VEGFR-2 (VEGFR-2/KDR) mRNA was expressed in basophils. These cells also expressed mRNA for the soluble form of VEGFR-1 and neuropilin (NRP)1 and NRP2. Flow cytometric analysis indicated that basophils express epitopes recognized by mAbs against the extracellular domains of VEGFR-2, NRP1, and NRP2. Our data suggest that basophils could play a role in angiogenesis and inflammation through the expression of several forms of VEGF and their receptors.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by grants from the Ministero dell’Istruzione, dell’Università e della Ricerca, the Istituto Superiore di Sanità (AIDS Project 40F.52), Ministero della Salute "Alzheimer Project," and Regione Campania.

² Address correspondence and reprint requests to Dr. Gianni Marone, Department of Clinical Immunology and Allergy, University of Naples Federico II, Via Sergio Pansini 5, 80131 Napoli, Italy. E-mail address: marone{at}unina.it

³ Abbreviations used in this paper: VEGF, vascular endothelial growth factor; CAM, chorioallantoic membrane; FPRL1, formyl peptide receptor like-1; FPRL2, FPR like-2; HSA, human serum albumin; NRP, neuropilin; PlGF, placental growth factor; PMN, polymorphonuclear cell; sVEGFR-1, soluble VEGFR-1; TRITC, tetramethylrhodamine isothiocyanate.