Expression and Function of the Vascular Endothelial Growth Factor Receptor FLT-1 in Human Eosinophils

Abstract

Vascular endothelial growth factor (VEGF) is highly expressed in the airway of patients with asthma. Whether VEGF affects eosinophil function in vitro and if VEGF receptors are involved was tested. Eosinophils were from venous blood of healthy donors. Cell migration was studied by micropore filter assays. Signaling mechanisms required for VEGF-dependent migration were tested using signaling enzyme blockers. Expression of flt-1 and KDR/flk-1 mRNA in eosinophils was demonstrated in reverse transcriptase-polymerase chain reaction, and receptor expression was investigated by fluorescence-activated cell sorting analysis. Eosinophil cationic protein release was measured in eosinophil supernatants by enzyme-linked immunosorbent assay. VEGF significantly stimulated eosinophil chemotaxis via activation of protein kinase C and phosphatidylinositol 3'-kinase. The effect on migration was reversed by an antibody against VEGF receptor flt-1, but not by an antibody against KDR/flk-1. Expression of VEGF receptor flt-1 mRNA was shown and synthesis of VEGF receptor in eosinophils is suggested by detection of VEGF receptor immunoreactivity on the cell surface. Data suggest that VEGF receptor flt-1 is expressed by eosinophils whose activation with VEGF stimulates directed migration and release of eosinophil cationic protein. Thus, VEGF may play an important role in the modulation of eosinophilic inflammation.

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

“…It appears that basophils, by expressing VEGF-2/KDR and not VEGFR-1/Flt-1, differ from the vast majority of monocytes (38,39,41,62), eosinophils (42), and neutrophils (43) that express VEGFR-1/Flt-1, and not VEGFR-2/KDR. VEGFR-1/Flt-1 appears to mediate chemotaxis in human monocytes (38,39), neutrophils (43), and eosinophils (42).…”

“…VEGFR-1/Flt-1 appears to mediate chemotaxis in human monocytes (38,39), neutrophils (43), and eosinophils (42). Endothelial cells express both VEGFR-1/Flt-1 and VEGFR-2/KDR (63), and whereas VEGFR-2/KDR activates cellular signaling, VEGFR-1/Flt-1 acts as a trap to sequester VEGF from VEGFR-2/KDR.…”

“…VEGF-A stimulates endothelial cell migration (48), and it is chemotactic for certain human immune cells (38,39,42,43). We evaluated the in vitro effects of a wide range of concentrations (5-500 ng/ml) of VEGF-A 165 on basophil chemotaxis.…”

Microglial VEGF Receptor Response Is an Integral Chemotactic Component in Alzheimer's Disease Pathology

“…Control animals were injected with control antibody rat IgG. The dose and treatment protocol for anti-Flt-1 Ab in this study have been previously reported to be effective in inhibition of Flt-1-mediated cellular responses (Feistritzer et al, 2004;Ambati et al, 2006).…”

“…In addition, the results from several studies have indicated that Flt-1-mediated signaling could contribute to pathological conditions in disease (Sköld et al, 2005). Elevated VEGF expression has been documented in asthma (Hoshino et al, 2001) and eosinophil inflammatory responses are dependent on activation of Flt-1 (Feistritzer et al, 2004). In a model of rheumatoid arthritis (RA), blockade of Flt-1 was effective in reducing symptoms of disease, whereas inhibition of the Flk-1 subtype of VEGF receptor was without effect (De Bandt et al, 2003).…”