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Immunoregulation of antigen presenting and secretory functions of monocytic cells by Helicobacter pylori antigens in relation to impairment of lymphocyte expansion

100%

Mnich E., Gajewski A., Rudnicka K., Gonciarz W., Stawerski P., Hinc K., Obuchowski M., Chmiela M.

2015

vol. 62

issue 4

641-650

The role of Helicobacter pylori (H. pylori) antigens in driving a specific immune response against the bacteria causing gastroduodenal disorders is poorly understood. Using a guinea pig model mimicking the natural history of H. pylori infection, we evaluated the effectiveness of immature and mature macrophages in promoting the blastogenesis of splenocytes from H. pylori infected and uninfected animals, in response to H. pylori antigens: glycine acid extract (GE), cytotoxin associated gene A protein (CagA), urease A (UreA) and lipopolysaccharide (LPS). Lymphocyte expansion was assessed in 72 h cell cultures, containing: immature or mature macrophages derived from bone marrow monocytes, unstimulated or stimulated with H. pylori antigens for 2 h. The proliferation was expressed as a ratio of [3H]-thymidine incorporation into DNA of antigen-stimulated to unstimulated cells and the DNA damage was determined by DAPI cell staining. TGF-β and IFN-γ were assessed immunoenzymatically in cell culture supernatants. Lymphocytes of control and H. pylori-infected animals proliferated intensively in response to phytohaemagglutinin (PHA) and in co-cultures with immature or mature macrophages treated with CagA or UreA (significantly) and GE (slightly) exluding the cultures containing H. pylori or E. coli LPS. This lymphocyte growth inhibition was related to DNA damage of monocytic cells in response to H. pylori or E. coli LPS and secretion of regulatory TGF-β, but not proinflammatory IFN-γ. Impaired homeostasis of monocytic cell function related to DNA damage and TGF-β release, in response to H. pylori LPS may lead to the suppression of adaptive immune response against the bacteria and development of chronic infection.

Helicobacter pylori increases expression of proapoptotic markers Fas and FasL on CD4 lymphocytes in children

75%

Kotłowska-Kmieć A., Bąkowska A., Szarszewski A., Kamińska B., Łuczak G., Radys W., Landowski P., Brodzicki J., Korzon M., Liberek A.

The pathomechanism of Helicobacter pylori action upon gastric mucosa and its role in the pathogenesis of gastritis have not been fully elucidated. The aim of this study was to evaluate the most prevalent lymphocyte subpopulations of the gastric mucosa in gastritis in children, as well as to evaluate the expression of Fas and Fas ligand receptors (FasL), periapoptotic markers of gastric mucosa lymphocytes before and after H. pylori eradication. Forty nine patients aged 6 to 17 years, investigated due to chronic abdominal pain, were studied. The obtained tissue samples were analysed by immunohistochemistry. Different lymphocyte subsets were quantified on the basis of surface antigen expression (CD3, CD4, CD8, CD20), secreted cytokines (IL-4, IL-6, IFNγ) and Fas and FasL proteins in the gastric mucosa. B and T helper lymphocytes were found to play a major role in the inflammatory infiltration in the gastric mucosa in children during H. pylori infection. Their expression was found to decrease after eradication. The enhanced expression of Fas receptor on lymphocytes before treatment and a decrease of this expression after eradication of H. pylori were shown. It was demonstrated that there is a correlation between CD4 and Fas receptor expression that may induce apoptosis of the helper lymphocytes in infected children.

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2 Acta Biochimica Polonica

1 2015

1 2009

1 Brodzicki J.

1 Bąkowska A.

1 Chmiela M.

1 Gajewski A.

1 Gonciarz W.

1 Hinc K.

1 Kamińska B.

1 Korzon M.

1 Kotłowska-Kmieć A.

1 Landowski P.

1 Liberek A.

1 Mnich E.

1 Obuchowski M.

1 Radys W.

1 Rudnicka K.

1 Stawerski P.

1 Szarszewski A.

1 Łuczak G.

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Immunoregulation of antigen presenting and secretory functions of monocytic cells by Helicobacter pylori antigens in relation to impairment of lymphocyte expansion

Helicobacter pylori increases expression of proapoptotic markers Fas and FasL on CD4 lymphocytes in children