Faculty Collaboration Database

TNF receptor I mediates chemokine production and neutrophil accumulation in the lung following systemic lipopolysaccharide. J Surg Res 2001 Dec;101(2):232-7

Date

12/12/2001

Pubmed ID

11735280

DOI

10.1006/jsre.2001.6274

Scopus ID

2-s2.0-0035679036 (requires institutional sign-in at Scopus site)   36 Citations

Abstract

BACKGROUND: Tumor necrosis factor (TNF)-alpha is a critical effector of lipopolysaccharide (LPS)-induced acute lung injury, and its effects are mediated by two structurally related receptors, RI and RII. Cellular adhesion molecules and C-X-C chemokines (Keratinocyte chemoattractant (KC) and macrophage inflammatory protein [MIP]-2) regulate tissue neutrophil polymorphonuclear neutrophil (PMN) accumulation in a multitude of inflammatory states. We hypothesized that TNFRI signaling dictates PMN accumulation in the lung via regulation of chemokine molecule production. Therefore, the purposes of this study were to (1) delineate LPS-induced lung TNF-alpha production and (2) characterize the contribution of both TNF receptors to lung chemokine production and neutrophil influx following systemic LPS.

METHODS: Wild-type or TNFRI and TNFRII knockout (KO) mice were injected with vehicle (saline) or LPS (Escherichia coli 0.5 mg/kg intraperitoneally). After 2, 4, 6, or 24 h, lungs were analyzed for TNF-alpha and chemokine (KC and MIP-2) protein expression (enzyme-linked immunosorbent assay) and PMN accumulation (myeloperoxidase assay).

RESULTS: There was an increase in total lung TNF-alpha (vehicle, 5.0 +/- 1.2 pg/mg total protein vs LPS, 950 +/- 318; P < 0.05) after LPS. Lung chemokine production and PMN accumulation were also increased compared to vehicle-injected mice. Lung chemokine production and PMN accumulation were significantly lower in TNFRI KO, but not TNFRII KO, mice, despite no difference in TNF-alpha production (TNFRI KO, 925 +/- 301 vs TNFRII KO, 837 +/- 267, P = 0.82).

CONCLUSIONS: Acute lung injury following systemic LPS administration is characterized by increased lung (1) TNF-alpha production, (2) C-X-C chemokine production, and (3) neutrophil accumulation. The maximal effect of LPS-induced lung neutrophil accumulation appears to be dependent upon the TNFRI receptor but not the TNFRII receptor. .

Author List

Calkins CM, Heimbach JK, Bensard DD, Song Y, Raeburn CD, Meng X, McIntyre RC Jr

Author

Casey Matthew Calkins MD Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Antigens, CD
Cell Movement
Chemokines
Lipopolysaccharides
Lung
Male
Mice
Neutrophils
Receptors, Tumor Necrosis Factor
Receptors, Tumor Necrosis Factor, Type I
Receptors, Tumor Necrosis Factor, Type II
Tumor Necrosis Factor-alpha