Faculty Collaboration Database

Toll-like receptor-4 signaling mediates pulmonary neutrophil sequestration in response to gram-positive bacterial enterotoxin. J Surg Res 2002 May 15;104(2):124-30

Date

05/22/2002

Pubmed ID

12020131

DOI

10.1006/jsre.2002.6422

Scopus ID

2-s2.0-0036349905 (requires institutional sign-in at Scopus site)   22 Citations

Abstract

BACKGROUND: Toll-like receptors (TLRs) serve as mediators of innate immune responses to pathogen-associated molecular patterns (PAMPs) which include lipopolysaccharide (LPS) and staphylococcal enterotoxin B (SEB). TLR-4 is thought to act as the primary effector of LPS recognition and TLR-2 is thought to mediate responses to Gram-positive bacterial proteins. Chemokines such as macrophage inflammatory protein (MIP-2) are peptides that are responsible for lung neutrophil (PMN) sequestration following an infectious or inflammatory insult. Given the Gram-positive origin of SEB, we hypothesized that mice with altered TLR-4 signaling would exhibit no difference in lung PMN sequestration following SEB when compared to wild-type mice.

METHODS: Wild-type and TLR-4 mutant mice were administered intratracheal saline, LPS (Escherichia coli 0.1 mg/kg), or SEB (1 mg/kg). After 24 h, lung PMN accumulation was determined by myeloperoxidase (MPO) assay and bronchoalveolar lavage fluid cell count (BALfcc). Total lung and BALf MIP-2 was measured by enzyme-linked immunosorbent assay.

RESULTS: There was an increase in lung PMN accumulation (by both MPO and BALfcc) and MIP-2 following LPS and SEB in wild-type mice compared to saline-treated controls. In contrast, TLR-4 mice failed to exhibit an increase in lung MIP-2 or PMN accumulation following either LPS or SEB compared to wild-type mice.

CONCLUSIONS: TLR-4 mutant mice are unresponsive to intratracheal LPS. SEB elicited an increase in lung MIP-2 and PMN accumulation in wild-type mice. However, TLR-4 mutant mice were protected from this process. This suggests that TLR-4 signaling may mediate the responses to other PAMPs in addition to LPS.

Author List

Calkins CM, Barsness K, Bensard DD, Vasquez-Torres A, 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
Bronchoalveolar Lavage Fluid
Chemokine CXCL2
Drosophila Proteins
Enzyme-Linked Immunosorbent Assay
Escherichia coli
Lipopolysaccharides
Lung
Male
Membrane Glycoproteins
Mice
Mice, Inbred C3H
Monokines
Neutrophils
Peroxidase
Pulmonary Alveoli
Receptors, Cell Surface
Signal Transduction
Toll-Like Receptor 2
Toll-Like Receptor 4
Toll-Like Receptors
Trachea