Neutrophil inhibitory factor prevents neutrophil-dependent lung injury.

Abstract

Neutrophil inhibitory factor (NIF) is a recently cloned 41-kDa protein from the canine hookworm that binds CD11b/CD18 and inhibits CD11b/CD18-dependent neutrophil adhesion. We evaluated NIF's effects on neutrophil-dependent lung injury in guinea pigs. Pulmonary vascular endothelial CD54 (ICAM-1) was induced in buffer-perfused lungs by 90-min exposure to 1000 U/ml TNF-alpha. Human neutrophils (2 x 10(7)) were added to the perfusate and activated by 5 x 10(-9) PMA; in some lungs, the neutrophils were pretreated with NIF (100 nM) before their addition to the perfusate. Lung injury was assessed by wet:dry weight ratio, and neutrophil uptake by lung myeloperoxidase (MPO) activity. HUVEC exposed to TNF-alpha for 90 min were assayed for neutrophil adhesion, and we compared PMA-stimulated neutrophil adhesion to endothelial cells and fibrinogen-coated plates. PMA-induced pulmonary edema (lung wet:dry ratio increased from 8.8 +/- 0.7 to 18.8 +/- 4.4) was inhibited by NIF (10.0 +/- 1.0). Lung MPO activity concomitantly decreased from 17.1 +/- 6.1 to 8.7 +/- 1.8 U/mg dry lung tissue in the NIF-treated group, similar to controls (6.9 +/- 2.0). Endothelial monolayer experiments confirmed that NIF reduced neutrophil adherence (basal adhesion of 11 +/- 3% increased to 30 +/- 5% with TNF-alpha pretreatment of endothelial cells, an increase that was reduced to 10 +/- 4% with NIF). Moreover, NIF prevented PMA-induced neutrophil adhesion to fibrinogen, a CD11b/CD18-dependent event, but produced a smaller decrease in adherence to endothelial cells, which also involves CD11a/CD18 integrins. These studies indicate that NIF prevents neutrophil-dependent lung vascular injury by inhibiting neutrophil adhesion to the TNF-alpha-activated endothelium.

• Authors: J W Barnard, M G Biro, S K Lo, S Ohno, M A Carozza, M Moyle, H R Soule, A B Malik
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 155 Issue 10 Pg. 4876-81 (Nov 15 1995) ISSN: 0022-1767 [Print] United States
• PMID: 7594491 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Glycoproteins
• Helminth Proteins
• Membrane Proteins
• Phorbol Esters
• Tumor Necrosis Factor-alpha
• Intercellular Adhesion Molecule-1
• NIF protein, Ancylostoma caninum

Topics

• Animals
• Cell Adhesion (drug effects)
• Cells, Cultured
• Dogs
• Endothelium (immunology, pathology)
• Glycoproteins (pharmacology)
• Guinea Pigs
• Helminth Proteins (pharmacology)
• Humans
• Intercellular Adhesion Molecule-1 (immunology)
• Lung (immunology, pathology)
• Male
• Membrane Proteins
• Neutrophil Activation
• Neutrophils (immunology, pathology)
• Phorbol Esters (pharmacology)
• Tumor Necrosis Factor-alpha (pharmacology)