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TNF alpha primes polymorphonuclear leukocytes for an enhanced respiratory burst to a similar extent as bacterial
R E Schopf1, R Keller, M Rehder
1Department of Dermatology, Johannes Gutenberg University, Mainz, West Germany.
Abstract:
We examined whether preincubating polymorphonuclear leukocytes (PMN) with TNF alpha would result in an enhanced respiratory burst upon subsequent stimulation by various agents. Bacterial lipopolysaccharide (LPS), a known primer of PMN, was used as control. We found that both LPS (0.01 to 10.0 microgram/ml) and recombinant TNF alpha (0.001 to 1.0 microgram/ml) act as direct stimulants of PMN as measured by chemiluminescence. Sixty minutes of preincubation of PMN with 1 microgram/ml TNF alpha or 10 micrograms/ml LPS resulted in similar priming for the respiratory burst elicited by opsonized zymosan, phorbol myristate acetate, zymosan, zymosan-activated serum, aggregated immunoglobulin, and f-met-leu-phe (FMLP) depending on the method of measurement used, i.e., chemiluminescence, production of O2-, and H2O2. Priming with TNF alpha for an enhanced response to stimulation by FMLP could be abrogated by anti-TNF alpha antibody. Cell-surface receptor numbers and binding-affinity constants for FMLP remained stable under conditions leading to priming. We conclude that TNF alpha is able to prime PMN for an enhanced respiratory burst to a similar extent as with LPS. Because PMN cell-surface receptors for FMLP are unaltered by priming, the enhanced respiratory burst seems to be due to changes in intracellular metabolism.
Insights
Tumor necrosis factor alpha (TNF alpha) primes polymorphonuclear leukocytes (PMN) for an enhanced respiratory burst, similar to lipopolysaccharide (LPS). This priming effect is due to intracellular metabolic changes, not altered cell-surface receptors.
Area of Science:
- Immunology
- Cellular Biology
Background:
- Polymorphonuclear leukocytes (PMN) are crucial immune cells.
- The respiratory burst is a key antimicrobial function of PMN.
- Tumor necrosis factor alpha (TNF alpha) is a cytokine with known immune-modulating effects.
Purpose of the Study:
- To investigate if TNF alpha can prime PMN for an enhanced respiratory burst.
- To compare the priming effects of TNF alpha with bacterial lipopolysaccharide (LPS).
- To elucidate the mechanism behind TNF alpha-induced PMN priming.
Main Methods:
- PMN were preincubated with varying concentrations of TNF alpha or LPS.
- The respiratory burst was measured using chemiluminescence, O2-, and H2O2 production.
- Stimulation was performed using various agents including opsonized zymosan and f-met-leu-phe (FMLP).
- Anti-TNF alpha antibody was used to abrogate priming effects.
- FMLP receptor numbers and binding affinities were assessed.
Main Results:
- Both TNF alpha and LPS directly stimulated PMN and acted as priming agents.
- Preincubation with TNF alpha or LPS resulted in similar priming for the respiratory burst.
- Priming effects of TNF alpha on FMLP stimulation were blocked by anti-TNF alpha antibody.
- Cell-surface FMLP receptor numbers and binding affinity remained unchanged during priming.
Conclusions:
- TNF alpha effectively primes PMN for an enhanced respiratory burst, comparable to LPS.
- The priming mechanism appears to involve alterations in intracellular metabolism rather than changes in FMLP cell-surface receptors.