Abstract
Mast cells have been shown to express vascular endothelial growth factor (VEGF), thereby implicating mast cells in pro-angiogenic processes. However, the mechanism of VEGF induction in mast cells and the possible expression of VEGF in fully mature mast cells have not been extensively studied. Here, we report that terminally differentiated peritoneal cell-derived mast cells can be induced to express VEGF in response to challenge with Staphylococcus aureus, thus identifying a mast cell–bacteria axis as a novel mechanism leading to VEGF release. Whereas live bacteria produced a robust upregulation of VEGF in mast cells, heat-inactivated bacteria failed to do so, and bacteria-conditioned media did not induce VEGF expression. The induction of VEGF was not critically dependent on direct cell–cell contact between bacteria and mast cells. Hence, these findings suggest that VEGF can be induced by soluble factors released during the co-culture conditions. Neither of a panel of bacterial cell-wall products known to activate toll-like receptor (TLR) signaling promoted VEGF expression in mast cells. In agreement with the latter, VEGF induction occurred independently of Myd88, an adaptor molecule that mediates the downstream events following TLR engagement. The VEGF induction was insensitive to nuclear factor of activated T-cells inhibition but was partly dependent on the nuclear factor kappa light-chain enhancer of activated B cells signaling pathway. Together, these findings identify bacterial challenge as a novel mechanism by which VEGF is induced in mast cells.
Highlights
Mast cells are tissue-resident cells located at the host–environment interface
vascular endothelial growth factor (VEGF) expression was modest after 2 h of co-culture and reached a maximum after 6 h
To approach the mechanism by with the bacteria induce VEGF expression in mast cells, we investigated the possibility that VEGF is induced by various toll-like receptor (TLR) ligands that are expressed by bacteria
Summary
Mast cells are tissue-resident cells located at the host–environment interface They express numerous immune receptors and host a multitude of immunological mediators [1,2,3]. While generally known for their involvement in allergy [4], mast cells have implicated in numerous additional pathological settings, ranging from defense against bacterial infections [5] to an involvement in malignant processes [6]. In the latter context, mast cells have, in particular, been implicated to support angiogenesis, thereby promoting tumor growth and metastasis [7, 8]. Mast cells have been shown to release VEGF in response to PGE2 activation through the EP[2] receptor [13], and the adenosine analog [5′-N-ethylcarboxamido adenosine (NECA)] has been reported to increase VEGF expression in human lung mast cells [14]
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