Priming of neutrophils and differentiated PLB-985 cells by pathophysiological concentrations of TNF-α is partially oxygen dependent

A. Paige Davis Volk, Brieanna M. Barber, Kelli L. Goss, Jake G. Ruff, Christine K. Heise, Jessica S. Hook, Jessica G. Moreland

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Activation of polymorphonuclear leukocytes (PMN) can be modulated to intermediate 'primed' states characterized by enhanced responsiveness to subsequent stimuli. We studied priming in response to TNF-α in human PMN and PLB-985 cells, a myeloid cell line differentiated to a neutrophilic phenotype (PLB-D). PMN generated reactive oxygen species (ROS) in response to TNF-α alone, and NADPH oxidase activity increased in response to stimulation with formyl-Met-Leu-Phe after priming. PLB-D cells also demonstrated priming of NADPH oxidase activity. Similar to priming by endotoxin, priming of the respiratory burst by TNF-α was predominantly oxygen dependent, with marked attenuation of ROS generation if primed anaerobically. Both PMN and PLB-D cells displayed significant increases in cell surface CD11b and gp91 phox expression after TNF-α priming and PMN displayed activation of MAPK. In response to TNF-α priming, neither mobilization of intracellular proteins nor activation of MAPK pathways was NADPH oxidase dependent. Priming of PMN and PLB-D cells by low TNF-α concentrations enhanced chemotaxis. These data demonstrate that pathophysiological concentrations of TNF-α elicit NADPH oxidase-derived ROS and prime cells for enhanced surface protein expression, activation of p38 and ERK1/2 MAPK pathways, and increased chemotaxis. Furthermore, PLB-D cells undergo TNF-α priming and provide a genetically modifiable model to study priming mechanisms.

Original languageEnglish (US)
Pages (from-to)298-314
Number of pages17
JournalJournal of innate immunity
Volume3
Issue number3
DOIs
StatePublished - Apr 1 2011

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Keywords

  • Chemotaxis
  • Cytokines
  • Endotoxin
  • NADPH oxidase
  • Oxidative burst
  • Reactive oxygen species
  • Sepsis

ASJC Scopus subject areas

  • Immunology and Allergy

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