Priming interleukin 8 production: Role of platelet-activating factor and p38

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

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


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 phosphospecific 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 stare 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.

Original languageEnglish
Pages (from-to)1348-1353
Number of pages6
JournalArchives of Surgery
Issue number12
StatePublished - Dec 1999


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