Tumor necrosis factor-α–stimulated polymorphonuclear leukocytes suppress migration and bactericidal activity of polymorphonuclear leukocytes in a paracrine manner

• Published in: Critical care medicine Vol. 30; no. 3; pp. 591 - 597
• Main Authors: Grutkoski, Patricia S, D’Amico, Ron, Ayala, Alfred, Hank Simms, H
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD by the Society of Critical Care Medicine and Lippincott Williams & Wilkins 01-03-2002; Lippincott
• Subjects: Analysis of Variance; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Cell Movement - immunology; Chemokines - metabolism; Emergency and intensive care: infection, septic shock; Humans; In Vitro Techniques; Intensive care medicine; Medical sciences; Neutrophil Activation - physiology; Neutrophils - immunology; Neutrophils - metabolism; Paracrine Communication - immunology; Phagocytosis - immunology; Receptor Cross-Talk - immunology; Receptors, IgG - metabolism; Tumor Necrosis Factor-alpha - immunology; Human; Pathophysiology; Migration; Cytokine; Granulocyte; Inflammation; Experimental study; In vitro; Bactericidal effect; Chemokine; Infection; Tumor necrosis factor α; Phagocytosis
• ISSN: 0090-3493; 1530-0293
• DOI: 10.1097/00003246-200203000-00017

OBJECTIVE Polymorphonuclear leukocytes (PMN) and tumor necrosis factor-α (TNF-α) play prominent roles in acute respiratory distress syndrome, ischemia-reperfusion injury, trauma, and sepsis. Whereas direct effects of TNF-α on PMN function and viability are well documented, little data are available addressing the ability of PMN to communicate with each other in response to cytokine stimulation. Therefore, the aim of this study was to determine whether TNF-α can modulate PMN function by inducing PMN to secrete products upon stimulation, which would affect other PMN in vitro in a manner independent of cell contact.
METHODS PMN were purified daily from blood obtained from a pool of 22 healthy volunteers. Conditioned media (CM-TNF) was prepared by incubating PMN in Hanks’ balanced salt solution plus TNF-α for 1–4 hrs. Freshly isolated PMN were resuspended in CM-TNF and analyzed for 1) phagocytosis of opsonized Escherichia coli, 2) oxidative metabolism as measured as an index of DCF-DA activation, and 3) migration to chemoattractants through Transwell inserts.
RESULTS CM-TNF decreased PMN phagocytotic activity by 8% to 15% and completely suppressed oxidative metabolism but did not modulate the expression of receptors associated with these functions. CM-TNF suppressed the migration of PMN to two biologically relevant agents, N-formyl-methionyl-leucyl-phenylalanine and leukotriene B4, by approximately 65%, but had no effect on PMN migration to interleukin-8. This suppression was observed for migration across plastic filters as well as extracellular matrix proteins.
CONCLUSION Our data demonstrate that PMN stimulated with TNF-α suppress the immunologic function and migration of other PMN independent of cell-cell contact and suggest that TNF-α may participate in a negative feedback loop by inducing a PMN-derived factor that counteracts its activity.