Published ahead of print on November 7, 2003, doi:10.1165/rcmb.2003-0314OC Am. J. Respir. Cell Mol. Biol., Volume 30, Number 5, May 2004, 729-735 A more recent version of this article appeared on May 1, 2004
Submitted on August 22, 2003 Expression and function of the vascular endothelial growth factor receptor FLT1 in human eosinophilsClemens Feistritzer1,1 Internal Medicine, University of Innsbruck, Innsbruck, Tyrol, Austria * To whom correspondence should be addressed. E-mail: christian.wiedermann{at}uibk.ac.at.
Vascular endothelial growth factor (VEGF) is highly expressed in the airway of asthmatic patients. 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 ELISA. 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 inflammtion.
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