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

Abstract

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 immune network in thyroid cancer

“…53,54 Interestingly, immune cells and tumors can produce pro-and anti-angiogenic isoforms of VEGFs. 62 A deeper knowledge of the balance between these isoforms could lead to the discovery of novel targets that can be manipulated to block TC growth.…”

“…59 MDSCs promote tumor angiogenesis through the release of VEGF-A and MMP-9. 60 Tie2 TEM, 61 human basophils 62 and human neutrophils are a source of proangiogenic factors, but their role in TC is unknown.…”

The underestimated role of basophils in Ph+ chronic myeloid leukaemia

“…However, basophils are also known to produce and secrete other angiogenic and fibrogenic cytokines, including VEGF‐A, VEGF‐B and Ang‐1 (Table 2). 59, 60, 61, 62 Moreover, immature CML basophils produce and release tryptase, a potent mitogen for fibroblasts and endothelial cells 63, 64, 65. Finally, histamine is known to regulate multiple endothelial cell functions, including angiogenesis 66, 67.…”

“…First, as mentioned, basophils are a rich source of vascular growth factors and may thus be able to contribute to stem cell‐niche expansion and increased angiogenesis. Moreover, basophils display many vascular permeability‐augmenting substances, including VEGF (identical with vascular permeability factor, VPF), HGF and histamine 58, 59, 60, 61, 62. These molecules may well facilitate stem cell redistribution from the BM into the circulation and also from the PB into extramedullary organs (Figure 3).…”

Immunomodulatory effects of VEGF: Clinical implications of VEGF-targeted therapy in human cancer

“…[2][3][4][5][6][7][8] VEGF is expressed by different cells (e.g., smooth muscle cells, endothelial cells, monocytes/macrophages, basophils, polymorphonuclear neutrophils and platelets) and exerts its biological effects through three protein-tyrosine kinases (VEGFR1, VEGFR2 and VEGFR3) and two nonprotein kinase co-receptors (neuropilin-1 and neuropilin-2). [2][3][4][5][6][7][8] VEGFR1 is a positive regulator of monocyte and macrophage migration, and has been described as a positive and negative regulator of VEGFR2 signaling capacity. Negative regulation is exerted, at least in part, by an alternatively spliced soluble VEGFR1 variant that binds to VEGF and thereby prevents VEGF from binding to VEGFR2.…”