Table 1.

Proteomic pathways associated with ARDS.

Pathway	Biomarker	Source	Role in ARDS	Reference
Endothelium injury and activation	VWF-Ag	Endothelial cells and platelets	Increase platelet binding to vascular endothelium	[17–22]
	Ang-2	Endothelial cells	Regulates capillary permeability	[21,23–26]
	ICAM-1	Endothelial cells, type 1 alveolar cells, leukocytes	Promotes leukocyte binding and transmigration	[27–31]
	E-selectin & P-selectin	Endothelial cells, platelets & leukocytes	Promotes leukocyte binding and transmigration	[32–34]
	VEGF	Endothelial cells	Increases vascular permeability	[35–39]
Epithelial injury	SP-A & SP-D	Type II alveolar cells	Impaired alveolar recruitment and innate immunity	[40–43]
	RAGE	Type I epithelial cells	Receptor for inflammatory ligands	[44,45]
	KL-6	Type II epithelial cells	Increased expression in injury or repair	[46]
Inflammation	IL-6	Leukocytes	Proinflammatory	[43,47–50]
	IL-8	Leukocytes	Proinflammatory	[43,47–50]
	IL-1β	Macrophages	Proinflammatory	[49]
	TNF-α	Macrophages	Proinflammatory	[49,51,52]
	sTNFr-I & II	Multiple tissues	Proinflammatory	[51–53]
	Neutrophils	Vascular migration	Promote phagocytosis and cellular injury	[54–56]
	MMP-9	Neutrophils	Mediate neutrophil cellular injury	[57]
	Macrophages	Resident in lung and vascular migration	Promote immunity and repair	[58]
	GM-CSF	Leukocytes and endothelial cells	Promote immunity and repair	[59]
Coagulation	Protein C	Liver	Prevents in-situ thrombosis	[23,30,60]
	PAI-I	Vascular endothelial cells and platelets	Promotes thrombosis	[23,30,48,60–62]
	Thrombomodulin	Type II pneumocytes	Activates protein C	[19,60]
Oxidative stress	Nitric oxide	Endothelial cells and leukocytes	Mediator of oxidative injury	[63]
	Ferritin	Acute phase reactant and product of oxidative stress	Mediator of oxidative injury	[64,65]
	Antioxidants	Ubiquitous	Prevent oxidative injury	[66]
Fibrosis	PCP I & III	Fibroblasts	Marker of collagen synthesis	[67–69]
Disordered repair	TGF-α	Ubiquitous	Endothelial cell migration and angiogenesis	[70,71]
	KGF & HGF	Mesenchymal cells	Epithelial cell mitogens
Apoptosis	Fas/Fas ligand	Ubiquitous	Promote cell death	[72–74]
	Perforin/granzyme	Ubiquitous	Promote cell death	[74]
Extracellular matrix	Desmosine	Lung interstitium	Marker of disruption of extracellular matrix	[75,76]

GM-CSF, granulocyte/macrophage colony stimulating factor; HGF, hepatocyte growth factor; ICAM-1, intercellular adhesion molecule 1; IL-1β, interleukin 1 beta; KGF, keratinocyte growth factor; PAI-I, plasminogen activator inhibitor-I; PCP I & III, procollagen peptides I & III; RAGE, receptor for advanced glycation end products; SPA & D, surfactant protein A & D; TGF-α transforming growth factor alpha; TNF-α, tumor necrosis factor alpha; vWF-Ag, von Willebrand factor antigen.