This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (13)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Surgical Cytokines  • Alert me on articles by topic  Social Bookmarking   What's this?

Role of Platelet-Activating Factor and p38

Saman Arbabi, MD; Matthew R. Rosengart, MD; Iris Garcia; Sandra Jelacic; Ronald V. Maier, MD

Arch Surg. 1999;134:1348-1353.

Hypothesis  Platelet-activating factor (PAF) activates p38, an important intracellular signal transduction kinase, and primes human mononuclear cells for the production of interleukin 8 (IL-8), a potent chemoattractant and activator of neutrophils.

Methods  Human mononuclear cells were isolated from healthy adults by Ficoll-paque density-gradient centrifugation. Interleukin-8 in the supernatant was measured by enzyme-linked immunosorbent assay. Dual phospho-specific p38 antibody was used to detect activated p38 by Western blotting.

Results  Lipopolysaccharide (LPS) and PAF activated p38. There was a shorter latency to peak p38 activation with PAF vs LPS stimulation, 5 vs 30 minutes. Platelet-activating factor–induced p38 activation was calcium dependent because it was inhibited by ethyleneglycoltetracetic acid. Lipopolysaccharide, 0.01 to 1.00 ng/mL, induced significant IL-8 production. Although PAF did not induce significant IL-8 production, it potentiated LPS-induced IL-8 production. Production of IL-8, in response to LPS alone or in combination with PAF, was inhibited by SB202190, a specific p38 inhibitor.

Conclusions  Although LPS and PAF activated p38, only LPS induced IL-8 production; PAF acted as a priming agent. It seems that p38 activation is necessary but not sufficient for IL-8 production by human mononuclear cells. Identifying and evaluating the activation state of inflammatory signal transduction pathways might lead to methods for controlling and preventing neutrophil-induced tissue injury without interfering with the normal host immune response.

From the Department of Surgery, University of Washington, Seattle.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Increased expression of p38 MAPK in human bronchial epithelium after lipopolysaccharide exposure
Roos-Engstrand et al.
Eur Respir J 2005;25:797-803.
ABSTRACT | FULL TEXT  

Porphyromonas gingivalis Lipopolysaccharide Is Both Agonist and Antagonist for p38 Mitogen-Activated Protein Kinase Activation
Darveau et al.
Infect. Immun. 2002;70:1867-1873.
ABSTRACT | FULL TEXT  

PAF-mediated Ca2+ influx in human neutrophils occurs via store-operated mechanisms
Hauser et al.
J. Leukoc. Biol. 2001;69:63-68.
ABSTRACT | FULL TEXT