Table I.

Effects of the virulence factor pyocyanin on the function of different mammalian cell types

Affected cell function	Target cells studied	Ref.
Airway epithelial cells
Inhibits Duox expression and activity	NHBE, NCI-H292	[47]
Inhibits ciliary beat frequency and mucociliary clearance	NHBE, HNE	[53,67]
	Guinea pig and baboon trachea	[68,69]
Inactivates V-ATPase, prevents vacuolar acidification	A549, HNE	[70,71]
Increases ICAM-1 expression	Mouse lung, A549	[62]
Inhibits plasma membrane localization of V-ATPase-dependent L-type-calcium channels and CFTR	16HBEo-	[71]
Activates NF-κB	JME/CF15	[72]
Impairs CFTR activity	CFBE41o-	[73]
Inactivates aconitase	A549	[74]
Inhibits cell growth	A549	[75]
Alters calcium signaling	A549, 16HBEo-	[76]
Triggers IL-8 expression and release	A549, Calu-3, ECFTE, C38, IB3	[58,62,63]
Inhibits TNFα-induced RANTES expression	A549	[63]
Inhibits catalase expression and activity	A549, NHBE	[77]
Inactivates α1 protease inhibitor	A549, 16HBEo-	[78]
Changes ultrastructure and MP in mitochondria	A549	[74]
Decreases ATP levels and SDH activity	A549	[74]
Directly oxidizes GSH	A549, 16HBEo-	[56]
Activates the caspase cascade	A549	[75]
Monocytes – Macrophages
Inhibits apoptotic neutrophil and Jurkat cell uptake	Human and mouse macrophages	[66]
Inhibits RNI production	Murine alveolar macrophages	[79]
Triggers IL-8 release	Sheep alveolar macrophages	[80]
Enhances LPS-triggered IL-1 and TNF-release	Human monocytes	[81]
Neutrophils (PMN)
Causes neutrophil influx into airway lumen	Mice, sheep lung	[55,80]
Dose-dependent effects on superoxide production	Human PMNs in vitro	[82,83]
Inhibition of superoxide production	Human PMNs in vitro	[47,84]
Lowers intracellular NADPH	Human PMNs in vitro	[57]
Suppresses killing of Staphylococcus aureus	Human PMNs in vitro	[57]
Induces apoptosis	Human, mouse PMNs	[64,65]
Increases intracellular diacylglyceride levels	Human PMNs in vitro	[84]
Inhibits LTB4 production and metabolism	Human PMNs in vitro	[85,86]
Induces release of vitamin B12-binding protein	Human PMNs in vitro	[83]
Lymphocytes
Inhibits IL-2 receptor expression and proliferation	Primary human cells	[87,88]
Inhibits antigen-induced differentiation	Primary human cells	[87,88]
Low concentrations stimulate, high concentrations inhibit T- and B-cell proliferation, Ig production of B cells, IL-2 production of T-cells and differentiation of B lymphocytes	Primary human cells	[81]
Endothelial cells
Loss of fenestration	Rat LSECs	[89]
Cellular damage	Porcine PPAE	[90]
Inhibits PGI2 release	Porcine PAE	[91]
Inhibits vasoregulatory effects of nitric oxide	Bovine PAE	[92]
Reduces intracellular GSH levels	HUVEC	[93]
Platelets
Reduces prostaglandin release	Human platelets	[94]

HNE, human nasal epithelial cells; PAE, pulmonary artery endothelial cells; NHBE, normal human bronchial epithelial cells; LSEC, liver sinusoidal endothelial cells; HUVEC, human umbilical vein endothelial cells; RNI, reactive nitrogen intermediates; MP, membrane potential; SDH, succinate dehydrogenase.