Figure 2.

Amplification of endothelial inflammatory response by cigarette smoke (CS) and bacterial products via innate immune upregulation. (A) Histamine secreted by the mast cell stimulates H1R on endothelial cells. CS may also increase histamine release. (B) H1R-mediated endothelial cell activation leads to increased expression of TLR2/TLR4 and nicotinic acetylcholine receptors (NAChR). This cross talk programs endothelial cells to become hyperresponsive to the TLR2/TLR4 ligands (PGN, LTA, and LPS) and CS leading to enhanced inflammatory response. (C) Increased TLR2/TLR4 signaling also increases H1R expression. Collective stimulation of newly expressed TLR2/TLR4 and H1R leads to robust proinflammatory changes in the endothelium and persistent vascular inflammation.