Expression and functions of the vascular endothelial growth factors and their receptors in human basophils.
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/10(6) 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.
de Paulis
Amato
A
Divisione di Immunologia Clinica ed Allergologia e Centro Interdipartimentale di Ricerca di Scienze Immunologiche di Base e Cliniche. Università di Napoli Federico II, Naples, Italy.
Prevete
Nella
N
Fiorentino
Isabella
I
Rossi
Francesca Wanda
FW
Staibano
Stefania
S
Montuori
Nunzia
N
Ragno
Pia
P
Longobardi
Amelia
A
Liccardo
Bianca
B
Genovese
Arturo
A
Ribatti
Domenico
D
Walls
Andrew F
AF
Marone
Gianni
G
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001491:Basophils / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D002464:Cell Migration Inhibition; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D002642:Chick Embryo; D005434:Flow Cytometry; D006636:Histamine Release / Q000276:immunology; D006801:Humans; D007700:Kinetics; D005810:Multigene Family; D009298:Nasal Polyps / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D039942:Neuropilin-1 / Q000096:biosynthesis / Q000235:genetics; D039943:Neuropilin-2 / Q000096:biosynthesis / Q000235:genetics; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D040262:Receptors, Vascular Endothelial Growth Factor / Q000096:biosynthesis* / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics* / Q000502:physiology; D042561:Vascular Endothelial Growth Factor B / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000096:biosynthesis; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D039943:Neuropilin-2; D020033:Protein Isoforms; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042561:Vascular Endothelial Growth Factor B; D039942:Neuropilin-1; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2