TNF-specific deactivation of granulocytes in vivo: a possible mechanism of self-protection

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A Simple and Efficient Method to Detect Nuclear Factor Activation in Human Neutrophils by Flow Cytometry
08:26

A Simple and Efficient Method to Detect Nuclear Factor Activation in Human Neutrophils by Flow Cytometry

Published on: April 9, 2013

B Schleiffenbaum1, L Olgiati, J Fehr

  • 1Department of Medicine, University Hospital, Zurich, Switzerland.

European Journal of Haematology
|November 1, 1992
PubMed

Insights

Tumor necrosis factor (TNF) can deactivate granulocytes (PMN), reducing their adhesion, granule release, and respiratory burst. This TNF-specific deactivation also affects adhesion molecule regulation and is observed in patients undergoing hemodialysis.

Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Granulocytes (polymorphonuclear leukocytes, PMN) exhibit specific deactivation towards tumor necrosis factor (TNF) after pre-exposure to TNF or other stimuli like endotoxin and complement C5a in vitro.
  • This deactivation phenomenon suggests a regulatory mechanism influencing PMN function in response to inflammatory signals.

Purpose of the Study:

  • To investigate the in vivo effects of TNF infusion on PMN function and receptor expression.
  • To determine if TNF-specific deactivation of PMN occurs in humans following TNF administration.
  • To examine TNF-specific cross-deactivation in patients exposed to activated complement during hemodialysis.

Main Methods:

  • Infusion of TNF (200 micrograms/m2) into a male volunteer.
  • Ex vivo analysis of PMN adhesion, secondary granule exocytosis, and respiratory burst activity (hexose monophosphate shunt activation).
  • Assessment of PMN surface adhesion molecules Mac-1 and LAM-1 expression.
  • Analysis of PMN from patients undergoing hemodialysis for TNF-specific cross-deactivation.

Main Results:

  • TNF infusion led to a significant, near-complete TNF-specific deactivation of PMN adhesion, exocytosis, and respiratory burst.
  • Up- and down-regulation of Mac-1 and LAM-1 surface molecules became resistant to TNF.
  • Deactivation correlated with a reduction in cellular TNF receptors.
  • PMN from hemodialysis patients exposed to activated complement demonstrated TNF-specific cross-deactivation.

Conclusions:

  • In vivo TNF administration induces a specific deactivation of PMN functions, mirroring in vitro findings.
  • This deactivation impacts key cellular processes including adhesion, degranulation, and oxidative burst.
  • TNF-specific cross-deactivation is observable in clinical settings involving complement activation, such as hemodialysis.

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