Activation of human macrophages by allogeneic islets preparations: inhibition by AOP-RANTES and heparinoids

Autor: Laurence Kessler, Christian Toso, Michel Pinget, Pascal Alain Robert Bucher, Alain Bohbot, K. Mandes, Séverine Sigrist, Jose Oberholzer, Roger Lamartine, Guy Esposito
Rok vydání: 2004
Předmět:
Chemokine
medicine.medical_treatment
Chemotaxis/drug effects/immunology
Receptors
CCR5/antagonists & inhibitors
Immunology and Allergy
Macrophage
Chemokine CCL5
Cells
Cultured
Macrophages/drug effects/immunology
Tumor Necrosis Factor-alpha/metabolism
Macrophage Activation/drug effects
ddc:617
Chemotaxis
Heparin
Middle Aged
Heparinoids/pharmacology
medicine.anatomical_structure
Cytokine
Heparinoids
CCR5 Receptor Antagonists
Interleukin-1/metabolism
medicine.drug
Adult
medicine.medical_specialty
Immunology
Dose-Response Relationship
Immunologic
Biology
Culture Media
Conditioned/pharmacology
Macrophage chemotaxis
Islets of Langerhans
Internal medicine
medicine
Humans
Islets of Langerhans/immunology
Aged
Tumor Necrosis Factor-alpha
Macrophages
Chemokine CCL5/analogs & derivatives/pharmacology
Pancreatic islets
Original Articles
Macrophage Activation
Molecular biology
Coculture Techniques
Transplantation
Endocrinology
Culture Media
Conditioned
biology.protein
Interleukin-1
Zdroj: Immunology, Vol. 111, No 4 (2004) pp. 416-21
ISSN: 1365-2567
0019-2805
DOI: 10.1111/j.1365-2567.2004.01828.x
Popis: During transplantation, pancreatic islets release chemokines which promote macrophage attraction, hampering engraftment of islets. The aim of this study was to modulate chemotaxis and the immune response of human macrophages induced by islets. Human monocyte-derived macrophages of healthy subjects were exposed to supernatants of human islets. Chemotaxis, tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) release were evaluated. To modulate migration, human macrophages were incubated in the presence of aminooxypentane-regulated on activation, normal, T-cell expressed, and secreted (AOP-RANTES), a potent antagonist of CCR5. Chemotactic activity of islets supernatant was modulated by the addition of heparin or heparinoids [pentosan and calix[8S]arene (C8S)]. AOP-RANTES significantly reduced, in a dose-dependent manner, macrophage chemotaxis and cytokine release induced by islets supernatant. The chemotactic index was reduced from 3.05 +/- 0.27 to 0.71 +/- 12, TNF-alpha from 1205 +/- 52 to 202 +/- 12 pg/ml, and IL-1beta from 234 +/- 12 to 10 +/- 6 pg/ml. The trapping of chemokines by heparinoids reduced the chemotactic activity of islets supernatant from 3.05 +/- 0.27 to 1.2 +/- 0.1 with heparin or pentosan and to 1.72 +/- 0.22 with C8S, and also decreased the TNF-alpha release by human macrophages from 1205 +/- 35 to 1000 +/- 26 (C8S), 250 +/- 21 (heparin) and 320 +/- 19 (pentosan) pg/ml, and IL-1beta from 234 +/- 13 to 151 +/- 5 (C8S), 50 +/- 3 (heparin) and 57 +/- 4 (pentosan) pg/ml. In conclusion, AOP-RANTES and heparinoids inhibit human macrophage activation and migration induced by islets supernatant.
Databáze: OpenAIRE
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