TNF-alpha priming effect on polymorphonuclear leukocyte reactive oxygen species generation and adhesion molecule

Jacek Rysz1, Maciej Banach, Robert A Stolarek

  • 12nd Department of Family Medicine, Medical University Hospital No. 2, Medical University of Łódź, Zeromskiego 113, 90-549 Łódź, Poland. jacek.rysz@skwam.lodz.pl

Abstract

Insights

Patients on hemodialysis show increased resting polymorphonuclear leukocyte (PMN) activity and receptor expression. However, their PMNs exhibit reduced responsiveness to TNF-alpha priming, indicating impaired immune function.

Area of Science:

  • Immunology
  • Nephrology
  • Cell Biology

Background:

  • Patients undergoing regular hemodialysis (HD) treatment may experience altered immune cell function.
  • Polymorphonuclear leukocytes (PMNs) play a crucial role in innate immunity and oxidative stress responses.

Purpose of the Study:

  • To investigate reactive oxygen species (ROS) generation in PMNs from hemodialysis patients.
  • To assess the expression of specific surface antigens on PMNs in patients undergoing regular HD treatment.

Main Methods:

  • Luminol-dependent chemiluminescence (CL) was used to measure PMN respiratory burst activity.
  • Flow cytometry was employed to determine the expression of CD11b/CD18, CD10, and CD13 receptors on PMNs.
  • PMNs were stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP), phorbol 12-myristate 13-acetate (PMA), opsonized zymosan (OZ), and TNF-alpha.

Main Results:

  • Basal PMN CL was significantly increased in HD patients compared to healthy controls.
  • While fMLP and OZ stimulation showed increased CL in HD patients, PMA-stimulated CL was similar to controls.
  • TNF-alpha-primed PMN CL was significantly lower in HD patients, indicating impaired priming.
  • Expressions of CD10 and CD13 receptors were elevated in HD patients, and CD11b expression was increased at rest and after fMLP stimulation, but CD18 expression was not significantly altered.

Conclusions:

  • HD patients exhibit enhanced basal PMN cytotoxicity and increased expression of adhesion and metalloproteinase receptors.
  • The study demonstrates a down-regulation of TNF-alpha-induced PMN priming in patients undergoing regular hemodialysis.
  • These findings suggest a complex modulation of PMN function in hemodialysis patients, with both enhanced and impaired aspects of immune response.