Faculty Collaboration Database

Platelet-activating factor priming of inflammatory cell activity requires cellular adherence. Surgery 2002 Aug;132(2):157-66

Date

09/10/2002

Pubmed ID

12219006

DOI

10.1067/msy.2002.125170

Scopus ID

2-s2.0-0036674393 (requires institutional sign-in at Scopus site)   7 Citations

Abstract

BACKGROUND: Platelet-activating factor (PAF) primes tissue-fixed inflammatory cells, but has no effect on circulating cells. Adherence of inflammatory cells leads to cytoskeletal reorganization, which is essential for optimal inflammatory function. The purpose of this study was to investigate whether cellular adherence plays a role in PAF priming of inflammatory cells.

METHODS: Differentiated THP-1 cells were maintained under adherent and nonadherent conditions. Selected cells were pretreated with PAF, followed by endotoxin stimulation. Cellular and nuclear proteins were analyzed by Western blot for components of the Toll-like receptor-mediated signaling cascade. Cytokine analysis was performed by enzyme-linked immunosorbent assay.

RESULTS: Endotoxin led to activation of interleukin (IL)-1-associated kinase, extracellular signal-regulated kinase 1/2 and p38, and nuclear translocation of nuclear factor-kappaB, all of which were significantly enhanced by previous cellular adherence. PAF led to priming only under adherent conditions, demonstrated by increased IL-1-associated kinase and extracellular signal-regulated kinase 1/2 activity; nuclear factor-kappaB translocation; and IL-6, IL-8, and tumor necrosis factor-alpha production over non-PAF-treated cells. PAF had no significant effect on p38 activity or IL-10 production under any condition.

CONCLUSIONS: PAF primes mononuclear cells by increasing Toll-mediated signaling only under adherent conditions. This, therefore, would limit PAF-induced priming in vivo to foci of stimulated adherent inflammatory cells with little effect systemically on circulating cells.

Author List

Cuschieri J, Gourlay D, Bulger E, Garcia I, Jelacic S, Maier RV

Author

David M. Gourlay BA, MD Chief, Professor in the Surgery department at Medical College of Wisconsin

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

Calcium
Carcinogens
Cell Adhesion
Cell Differentiation
Humans
In Vitro Techniques
Inflammation Mediators
Interleukin-1 Receptor-Associated Kinases
Lipopolysaccharides
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases
Monocytes
NF-kappa B
Phosphorylation
Platelet Activating Factor
Platelet Membrane Glycoproteins
Protein Kinases
Receptors, Cell Surface
Receptors, G-Protein-Coupled
Tetradecanoylphorbol Acetate
Vitamin D
p38 Mitogen-Activated Protein Kinases