Increased synthesis of vascular endothelial growth factor in allergic airway inflammation in histidine decarboxylase knockout (HDC(-/-)) mice.
Histamine and vascular endothelial growth factor (VEGF) have been implicated in the pathogenesis of allergic asthma; they enhance inflammation, vascular permeability, and mucus secretion. Histamine was suggested to alter the level of VEGF via the H2 receptors. Here the authors have applied histidine decarboxylase gene-targeted (HDC(-/-)) mice, lacking histamine, to investigate the effect of histamine deficiency on VEGF expression in an animal model of asthma. HDC(-/-) and wild-type (WT) mice were sensitized and challenged with ovalbumin (OVA). VEGF mRNA expression and protein level were determined in the lung. Number of VEGF-positive immune cells of bronchoalveolar lavage (BAL) and their intracellular VEGF content were measured by flow cytometry. VEGF protein level in the lung and in the BAL cells was increased in OVA treated (HDC(-/-)(ova) as well as in WT(ova)) animals compared to their controls. However, there was no difference in the VEGF levels between HDC(-/-) or WT animals, either in the lung or in the BAL cells. In conclusion, increased VEGF production of the lung or BAL immune cells can be induced by allergen provocation independently from the genetic background of the animals. These data suggest that VEGF-mediated allergic processes can persist in the absence of histamine.
Sziksz
Erna
E
First Department of Paediatrics, Semmelweis University, Budapest, Hungary. sziksz@gyer1.sote.hu
Tibor Kozma
Gergely
G
Komlósi
Zsolt István
ZI
Pállinger
Eva
E
Kardos
Magdolna
M
Szebeni
Beáta
B
Losonczy
György
G
Falus
András
A
Szabó
András
A
Tulassay
Tivadar
T
Vannay
Adám
A
D000818:Animals; D001249:Asthma / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D005260:Female; D006632:Histamine / Q000378:metabolism*; D006640:Histidine Decarboxylase / Q000235:genetics*; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin; D042442:Vascular Endothelial Growth Factors / Q000032:analysis / Q000378:metabolism*
D042442:Vascular Endothelial Growth Factors; D006632:Histamine; D010047:Ovalbumin; D006640:Histidine Decarboxylase