Expression of vascular permeability factor (VPFNEGF) messenger RNA by plasma cells: Possible involvement in the development of edema in chronic inflammation

Abstract

Edema occurs in some types of chronic inflammation such as nasal polyps, uterine cervical polyps and gastric hyperplastic polyps. However, the factors or cellular components involved in the development of edema in chronic inflammation remain to be clarified. Recently, the gene encoding vascular permeability factor (VPF) or vascular endothelial growth factor (VEGF) and the genes encoding its receptors (kinase insert domain-containing receptor (KDR) and fms-like tyrosine kinase-1 [fit-1]) have been cloned. VPF/VEGF induces vascular hyperpermeability and vascular endothelial proliferation through KDR or fit-1 receptors. As there is a possibility that VPF/VEGF may play a role in the development of edema in chronic inflammation, we examined the messenger (m) RNA expression of VPF/VEGF and its receptors in nasal polyp tissues, which is an example of chronic inflammation with remarkable edema. Using northern blotting, all nasal polyp tissues examined expressed mRNA of VPF/VEGF and KDR. In situ hybridization revealed that VPF/VEGF mRNA-expressing cells were scattered in the edematous stroma of nasal polyps. In the adjacent sections, these cells showed the morphological features of plasma cells and expressed mRNA of immunoglobulin light chains. Human B cell leukemia and plasmacytoma cell lines expressed VPF/VEGF mRNA but human mast-cell leukemia and T cell leukemia cell lines did not. The alternatively spliced pattern of VPF/VEGF transcripts observed in nasal polyp tissues was consistent with that in plasmacytoma cell lines. Taken together, the VPF/VEGF mRNA-expressing cells in nasal polyps appeared to be plasma cells, suggesting that plasma cells may play an important role in the development of edema in chronic inflammation through the production of VPF/VEGF.

Vascular endothelial growth factor induces growth of uterine cervix and immune cell recruitment in mice

“…For instance, antagonism of VEGF action in brain or stroke injury-induced edema significantly reduces swelling and hyper-permeability of brain microvasculature (Roberts & Palade 1995, Van Bruggen et al 1999, Dafni et al 2002. In nasal polyps, expression of VEGF and KDR is localized in plasma cells and appears to be involved in signal transduction (Ito et al 1995). Other conditions that may induce expression of VEGF in the brain, which in turn induces cerebrovascular permeability, include hypoxia and ischemic brain injuries (Van Bruggen et al 1999).…”

Vascular endothelial growth factor receptor Flt-1 negatively regulates developmental blood vessel formation by modulating endothelial cell division

“…[66][67][68][69][70] Thus, flt-1 could potentially negatively modulate pathologic vascularization, as described here for vascular development, and therapeutics that specifically block flt-1 action may help rather than hinder pathologic vascularization. Conversely, VEGF treatment can in some cases promote vascularization of ischemic limbs, 71,72 but our lack of understanding about how VEGF signaling is normally exquisitely fine-tuned has hampered our ability to produce functional vessels therapeutically.…”

Vascular endothelial growth factor gene and protein: strong expression in thyroiditis and thyroid carcinoma

“…These properties outline a very important role in physiological angiogenesis (Brown et al 1997, Ferrara & Keyt 1997, Kamat et al 1995. VEGF has also been implicated in diabetic retinopathy (Aiello et al 1994), various inflammatory diseases (Fava et al 1994, Koch et al 1994, Brown et al 1995a and tumor growth (Plate et al 1992, Senger et al 1993, Dvorak et al 1995, Ito et al 1995, Brown et al 1997, Ferrara & Davis-Smyth 1997. VEGF is a potent mitogen (ED 50 2-10 pM) for endothelial cells, without significant mitogenic activity for other types of cells (Ferrara & Keyt 1997).…”