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
05/22/2002Pubmed ID
12020131DOI
10.1006/jsre.2002.6422Scopus ID
2-s2.0-0036349905 (requires institutional sign-in at Scopus site) 22 CitationsAbstract
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 JrAuthor
Casey Matthew Calkins MD Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBronchoalveolar 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