In vitro – transcriptional response of polymorphonuclear leukocytes following contact with different antigens

Abstract

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.

Transcriptomics: A Step behind the Comprehension of the Polygenic Influence on Oxidative Stress, Immune Deregulation, and Mitochondrial Dysfunction in Chronic Kidney Disease

“…Surprisingly, these results were different from those published by Hochegger et al [ 76 ] that did not find any significant genetic difference between human polymorphonuclear neutrophils (PMN) stimulated with cuprophane versus polysulfone. When these results were combined to one group, the comparison with unstimulated cells revealed 50 genes differentially expressed with a marked upregulation of FOS- and JUN-transcripts, but with only little activation of immune response genes, and, contrarily to PMN stimulated with E. Coli, no upregulation of apoptosis related transcripts.…”

Effector responses of bovine blood neutrophils against Escherichia coli: Role of NOD1/NF-κB signalling pathway

“…In the face of microbial insult, neutrophils are capable of extensive and rapid gene expression changes that are important in the regulation of many neutrophil functions, as well as modulation of the immune response (Hochegger et al, 2007;Newburger et al, 2000;Subrahmanyam et al, 2001;Zhang et al, 2004). NF-B is a key transcriptional regulator of the genes encoding many proinflammatory cytokines and chemokines (Hayden and Ghosh, 2011).…”