Epidermal growth factor enhances TNF-alpha-induced priming of human neutrophils.
The intensity of neutrophil inflammatory response could be rapidly amplified by priming with pro-inflammatory mediators such as TNF-alpha, GM-CSF or LPS at low concentrations prior to stimuli. We proposed that epidermal growth factor (EGF) increases TNF-alpha-induced priming of human neutrophils. This study showed that EGF enhanced TNF-alpha-induced activation of neutrophils functions. The addition of EGF to neutrophils cultured with TNF-alpha resulted in increased respiratory burst and phagocytic activity of polymorphonuclear leukocytes (PMN) and up-regulation of adhesion molecule CD11b. Moreover, EGF enhanced IL-8 production by TNF-alpha-primed PMN. EGF alone was able to prime CD11b expression and IL-8 production by PMN. EGF receptor selective tyrosine kinase inhibitor, tyrphostin AG-1517, blocked the effect of priming with EGF, whereas the status of non-primed and TNF-alpha-primed neutrophils remained unaffected. EGFR expression on neutrophils was confirmed by flow cytometry and CELISA methods. These data provide the original evidence that EGF significantly enhances TNF-alpha-induced priming of human neutrophils acting through EGFR tyrosine kinase pathway. The observed effect may be a result of co-operative action of EGF, TNF-alpha and reactive oxygen intermediates (ROI).
Lewkowicz
Przemysław
P
Department of Clinical Immunology, Institute of Polish Mother's Memorial Hospital, ul. Rzgowska 281/289, 93-338 Lodz, Poland. natalewk@wp.pl
Tchórzewski
Henryk
H
Dytnerska
Katarzyna
K
Banasik
Małgorzata
M
Lewkowicz
Natalia
N
D039481:CD11b Antigen / Q000378:metabolism; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology / Q000502:physiology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D010587:Phagocytosis / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology*; D020032:Tyrphostins / Q000494:pharmacology
C108081:AG 1517; D039481:CD11b Antigen; D016209:Interleukin-8; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D020032:Tyrphostins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors