Tumor necrosis factor-alpha-stimulated polymorphonuclear leukocytes suppress migration and bactericidal activity of

Patricia S Grutkoski1, Ron D'Amico, Alfred Ayala

  • 1Division of Surgical Research, Rhode Island Hospital, and Brown University School of Medicine, Providence, USA.

Abstract

Insights

Tumor necrosis factor-alpha (TNF-alpha) stimulation induces polymorphonuclear leukocytes (PMN) to release factors that suppress the function and migration of other PMN. This suggests TNF-alpha may create a negative feedback loop in immune responses.

Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Polymorphonuclear leukocytes (PMN) and tumor necrosis factor-alpha (TNF-alpha) are key players in inflammatory conditions like sepsis and acute respiratory distress syndrome.
  • While TNF-alpha's direct effects on PMN are known, how PMN communicate with each other upon cytokine stimulation is less understood.

Purpose of the Study:

  • To investigate if TNF-alpha can modulate PMN function by inducing PMN to secrete factors that affect other PMN independently of cell contact.

Main Methods:

  • PMN were isolated from healthy volunteers.
  • Conditioned media (CM-TNF) was created by incubating PMN with TNF-alpha.
  • Fresh PMN were exposed to CM-TNF and assessed for phagocytosis, oxidative metabolism, and migration.

Main Results:

  • CM-TNF reduced PMN phagocytosis by 8-15% and completely suppressed oxidative metabolism.
  • PMN migration to N-formyl-methionyl-leucyl-phenylalanine and leukotriene B4 was suppressed by ~65%, but not to interleukin-8.
  • These suppressive effects occurred independently of cell-cell contact.

Conclusions:

  • TNF-alpha-stimulated PMN release factors that suppress the immune function and migration of other PMN.
  • This suggests a potential negative feedback mechanism where TNF-alpha induces a PMN-derived factor that counteracts its own activity.

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