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Mononuclear cell adherence induces neutrophil chemotactic factor/interleukin-8 gene expression
K Kasahara1, R M Strieter, S W Chensue
1Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602.
Journal of Leukocyte Biology
|September 1, 1991
Summary
Cell adherence triggers interleukin-8 (IL-8) production in peripheral blood mononuclear cells (PBMC), a key step in initiating inflammation and attracting polymorphonuclear cells (PMN) for host defense.
Area of Science:
- Immunology
- Cell Biology
- Inflammation Research
Background:
- Polymorphonuclear cells (PMN) accumulation is crucial for inflammatory responses and host defense.
- PMN migration from blood vessels to tissues begins with endothelial adherence.
Purpose of the Study:
- To investigate the role of peripheral blood mononuclear cell (PBMC) adherence in interleukin-8 (IL-8) production.
- To understand the signaling pathways involved in adherence-induced IL-8 expression.
Main Methods:
- Northern blot analysis to quantify IL-8 mRNA levels in adherent and non-adherent PBMC.
- Immunochemistry and chemotaxis assays to measure IL-8 protein and bioactivity.
- Treatment with actinomycin-D, cycloheximide, and neutralizing antibodies (anti-IL-1β, anti-TNF-α).
Main Results:
- PBMC adherence to plastic significantly increased IL-8 mRNA expression, peaking at 8 hours.
- Non-adherent PBMC showed minimal IL-8 mRNA levels compared to adherent cells.
- Adherent PBMC produced bioactive and antigenic IL-8, with maximal levels by 24 hours.
- IL-8 gene expression was suppressed by inhibitors of RNA and protein synthesis but not by IL-1β or TNF-α neutralizing antibodies.
Conclusions:
- PBMC adherence acts as a critical signal for IL-8 production.
- IL-8 induction by adherence is essential for initiating the inflammatory response via PMN recruitment.
- The findings elucidate a key mechanism in the early stages of inflammation.