Advertisement
Table 1 Therapeutic inhibition of neutrophil-dependent processes in 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) |
