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Table 1 Therapeutic inhibition of neutrophil-dependent processes in acute lung injury.

From: Contribution of Neutrophils to Acute Lung Injury

Target molecule

Animal model

Effect

Ref.

Cytokines

   

TNF

Ab against TNF; Ischemia/reperfusion-induced ALI

Not protective

(96)

TNF

TNF-α-converting enzyme inhibition in acute lung injury induced by endotoxin in the rat

Protective

(95)

Chemokines and their receptors

   

IL-8

Inhibition of IL-8 in acid aspiration-induced ALI in rabbits

Protective

(72)

IL-8

Inhibition of IL-8; pancreatitis-induced ALI in rabbits

Protective

(70)

IL-8

Inhibition of IL-8 in oleic acid + endotoxin-induced ALI

Protective

(73)

IL-8

Inhibition of IL-8 in an ischemia-reperfusion injury

Protective

(71)

CXCR2

competitive blockade of CXCR2 in hyperoxia-induced ALI in rats

Protective

(79)

CXCR2

Inhibition of CXCR2 in acute pancreatitis-associated lung injury

Protective

(76)

CXCR2

Inhibition of CXCR2 in ischemia-reperfusion injury

Protective

(80)

CXCR2

Inhibition of CXCR2 in a rabbit model of Gram-positive enterotoxemia

Protective

(211)

CXCR2

Bleomycin-induced ALI

Protective

(212)

CXCR2

LPS- and acid-induced ALI

Protective

(75)

CINC

Neutralizing Ab to CINC (cytokine induced neutrophil chemo-attractant; homolog of human GRO-α) in acute pancreatitis-associated lung injury

Protective

(213)

Cell adhesion molecules

   

P-selectin

Inhibition of P-selectin in a burn injury model of ALI in sheep

Not protective

(39)

P-selectin

Inhibition of P-selectin with Ab in cobra venom factor (CVF)-induced ALI

Protective

(46)

P-selectin

Inhibition with sialyl Lewis X-oligosaccharide in a LPS-induced ALI in rabbits

Protective

(44)

P-selectin

Blocking P-selectin in acid aspiration ALI

Protective

(47)

E- and L-selectin

Sepsis-induced ALI in Yorkshire swine; dual-binding antibody to E- and L-selectin, EL-246

Protective

(45)

Integrins (αvβ5 and αvβ6)

IL-1β-induced ALI in mice (blocking Ab against avb5 and avb6 integrins)

Protective

(51)

β2-integrins (CD11/CD18)

Blocking β2-integrins in a transfusion-induced ALI

Not protective

(38)

β2-integrins (CD11/CD18)

CVF-induced ALI in rats; Ab against CD11 or CD18

Protective

(55)

β2-integrins (CD11/CD18)

Inhaled LPS

Protective

(54)

β2-integrin

β2-integrin blockade in Escherichia coli (E. coli)-induced lung injury in mice

Protective

(56)

ICAM-1

Inhibition of ICAM-1 in CVF-induced ALI; interestingly ICAM1–/– displayed no protective effect

Protective

(46)

Granule proteins

   

Neutrophil elastase

Sivelestat, a specific neutrophil elastase inhibitor; phorbol myristate acetate-induced ALI in conscious rabbits

Protective

(113)

Neutrophil elastase

Delayed neutrophil elastase inhibition in ALI induced by endotoxin inhalation in hamsters

Protective

(114)

Neutrophil elastase

ONO-5046, a competitive, reversible, and specific neutrophil elastase inhibitor in ALI induced by air embolism in awake sheep

Not protective

(115)

Neutrophil elastase

ONO-5046 in ALI-induced by E. coliendotoxin in pigs

Protective

(116)

MMP 8

Specific MMP-8 inhibitor in ventilator-induced ALI

Protective

(152)

MMP 9

MMP inhibitor (6-demethyl-6-deoxy-4-dedimethylamino-tetracycline) treatment for 3 d in ventilator-induced lung injury in rats

Protective

(149)

Radical release

   

NADPH oxidase

NADPH oxidase inhibitor apocynin in sepsis-induced lung injury in guinea pigs

Protective

(206)

Nitric oxide synthase

LPS-induced ALI

Protective

(207)