In vitro--transcriptional response of polymorphonuclear leukocytes following contact with different antigens.
Background Human polymorphonuclear neutrophils (PMN) are activated and undergo apoptosis if brought into contact with cuprophane haemodialysis membranes, a phenomenon not observed if more 'biocompatible' polysulfone dialysers are used. It remains yet to be defined if this differential response is due to mechanisms regulated on a transcriptional or protein level. Furthermore, it is not clear if the contact of PMN with membranes ('frustrated' phagocytosis) activates the same response as phagocytosis of bacteria (complete phagocytosis). Materials and methods We performed a genome-wide differential gene expression study using cDNA microarrays to analyse the impact of different dialysis fibres on the transcriptional response of PMN of human healthy volunteers. These results were compared to transcriptional response of PMN during phagocytosis of Escherichia coli. Results We did not detect significant differences in gene expression between PMN stimulated with cuprophane or pulysulfone. Compared to unstimulated PMN the 'frustrated' phagocytosis of either dialysis membrane resulted in increased expression of 50 genes, with a marked up-regulation of FOS - and JUN - transcripts, but with only little activation of immune response genes, and virtually no activation of apoptosis related RNA transcripts. In contrast, phagocytosis of E.coli was associated with a striking up-regulation of 88 genes, most of them involved in pro- and antiapoptotic pathways, immune response and activation of nuclear factor kappa B and inhibitor of NF-kappa B. Conclusions Our results suggest that the response of PMN to artificial surfaces is not controlled on transcriptional level. Complete and 'frustrated' phagocytosis activate markedly distinct transcriptional regulatory pathways in PMN.
Hochegger
K
K
Division of Nephrology, Medical University Innsbruck, Anichstrasse 35, Innsbruck, Austria.
Perco
P
P
Enrich
J
J
Mayer
B
B
Mayer
G
G
Rosenkranz
A R
AR
Rudnicki
M
M
D000941:Antigens / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology; D001672:Biocompatible Materials / Q000494:pharmacology*; D015153:Blotting, Western / Q000379:methods; D002482:Cellulose / Q000031:analogs & derivatives* / Q000494:pharmacology; D004926:Escherichia coli; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D046228:Microarray Analysis / Q000379:methods; D016328:NF-kappa B / Q000378:metabolism; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology; D011108:Polymers / Q000494:pharmacology*; D017382:Reactive Oxygen Species; D013450:Sulfones / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects
D000941:Antigens; D001672:Biocompatible Materials; D016328:NF-kappa B; D011108:Polymers; D017382:Reactive Oxygen Species; D013450:Sulfones; C017662:polysulfone P 1700; D002482:Cellulose; C009865:cuprammonium cellulose