The Age of Louis XIV : A History of European Civilization in the Period of Pascal . Molière, Cromwell,, Milton, Peter the Great, Newton, and Spinoza :

X, 802 tr.; 24 cm

The Age of Voltairel Heritage : A History of Civilization in Western Europe from 1715 to 1756, with Special Emphasis on the Conflict Between Religion

X, 898 tr.; 24 cm

Rousseau and Revolution : A History of Civilization in France, England, and Germany from 1756 and in the Remainder of Europe from 1715, to 1789

XX, 1091 tr.; 24 cm

The Age of Napoleon : A History of European Civilization from 1789 to 1815

XX, 872 tr.; 24 cm

The Age of Reason Begins : A History of European Civilization in the Period of Shakespeare . Bacon, Montaigne, Rembrandt, Galileo, and Descartes : 1558

X, 729 tr.; 24 cm

The story of civilization : The age of Louis XIV

345 tr. : minh họa ; 22 cm

The story of civilization : The age of Louis XIV

429 tr. : minh họa ; 22 cm

The story of civilization : The age of Louis XIV

444 tr. : minh họa ; 22 cm

The story of civilization.

Mode of access: Internet

Proteinase 3 on apoptotic cells disrupts immune silencing in autoimmune vasculitis

Granulomatosis with polyangiitis (GPA) is a systemic necrotizing vasculitis that is associated with granulomatous inflammation and the presence of anti-neutrophil cytoplasmic antibodies (ANCAs) directed against proteinase 3 (PR3). We previously determined that PR3 on the surface of apoptotic neutrophils interferes with induction of antiinflammatory mechanisms following phagocytosis of these cells by macrophages. Here, we demonstrate that enzymatically active membrane-associated PR3 on apoptotic cells triggered secretion of inflammatory cytokines, including granulocyte CSF (G-CSF) and chemokines. This response required the IL-1R1/MyD88 signaling pathway and was dependent on the synthesis of NO, as macrophages from animals lacking these pathways did not exhibit a PR3-associated proinflammatory response. The PR3-induced microenvironment facilitated recruitment of inflammatory cells, such as macrophages, plasmacytoid DCs (pDCs), and neutrophils, which were observed in close proximity within granulomatous lesions in the lungs of GPA patients. In different murine models of apoptotic cell injection, the PR3-induced microenvironment instructed pDC-driven Th9/Th2 cell generation. Concomitant injection of anti-PR3 ANCAs with PR3-expressing apoptotic cells induced a Th17 response, revealing a GPA-specific mechanism of immune polarization. Accordingly, circulating CD4+ T cells from GPA patients had a skewed distribution of Th9/Th2/Th17. These results reveal that PR3 disrupts immune silencing associated with clearance of apoptotic neutrophils and provide insight into how PR3 and PR3-targeting ANCAs promote GPA pathophysiology