Caspase-8 is activated by cathepsin D initiating neutrophil apoptosis during the resolution of inflammation

In the resolution of inflammatory responses, neutrophils rapidly undergo apoptosis. We describe a new proapoptotic pathway in which cathepsin D directly activates caspase-8. Cathepsin D is released from azurophilic granules in neutrophils in a caspase-independent but reactive oxygen species-dependent manner. Under inflammatory conditions, the translocation of cathepsin D in the cytosol is blocked. Pharmacological or genetic inhibition of cathepsin D resulted in delayed caspase activation and reduced neutrophil apoptosis. Cathepsin D deficiency or lack of its translocation in the cytosol prolongs innate immune responses in experimental bacterial infection and in septic shock. Thus, we identified a new function of azurophilic granules that is in addition to their role in bacterial defense mechanisms: to regulate the life span of neutrophils and, therefore, the duration of innate immune responses through the release of cathepsin D.

Distinct roles of vascular endothelial growth factor-D in lymphangiogenesis and metastasis

In many human carcinomas, expression of the lymphangiogenic factor vascular endothelial growth factor-D (VEGF-D) correlates with up-regulated lymphangiogenesis and regional lymph node metastasis. Here, we have used the Rip1Tag2 transgenic mouse model of pancreatic beta-cell carcinogenesis to investigate the functional role of VEGF-D in the induction of lymphangiogenesis and tumor progression. Expression of VEGF-D in beta cells of single-transgenic Rip1VEGF-D mice resulted in the formation of peri-insular lymphatic lacunae, often containing leukocyte accumulations and blood hemorrhages. When these mice were crossed to Rip1Tag2 mice, VEGF-D-expressing tumors also exhibited peritumoral lymphangiogenesis with lymphocyte accumulations and hemorrhages, and they frequently developed lymph node and lung metastases. Notably, tumor outgrowth and blood microvessel density were significantly reduced in VEGF-D-expressing tumors. Our results demonstrate that VEGF-D induces lymphangiogenesis, promotes metastasis to lymph nodes and lungs, and yet represses hemangiogenesis and tumor outgrowth. Because a comparable transgenic expression of vascular endothelial growth factor-C (VEGF-C) in Rip1Tag2 has been shown previously to provoke lymphangiogenesis and lymph node metastasis in the absence of any distant metastasis, leukocyte infiltration, or angiogenesis-suppressing effects, these results reveal further functional differences between VEGF-D and VEGF-C.

Catalogue of the governors, trustees, and officers , and of the alumni and other graduates, of Columbia College (originally King's College), in the city of New York, from 1754 to 1864.

Includes index.

New York illustrated : presented to members of the National Division, Sons of Temperance of North America, by the Grand Division of Eastern New York at the 29th annual session, New York City, June 18, 1873 /

Mode of access: Internet.

Chris, the model maker; a story of New York,

Mode of access: Internet.

Romantic biography of the age of Elizabeth; or, Sketches of life from the bye-ways of history.

v. 1. Introduction. Margaret of Valois, Queen of Henry IV. Robert Dudley, Earl of Leicester. Castelnau, Ambassador from France. La Mothe Fenelon. La Mothe Fenelon and Castelnau. Thomas Howard, fourth duke of Norfolk. Hugh, Earl of Tyrone, and notices of Walter, 1st Earl of Essex. Dr. Dee.--v. 2. Calvin and the church of Geneva. William Whittingham and the Puritans. Archbishop Whitgift and Dr. Cartwright. John Darrel, the exorcist. Loyola and the order of the Jesuits. Robert Parsons, Edmund Campian, and the Jesuits in England. Pope Sixtus V. Charles de Valois, Duc d'Angoulême. Henry de la Tour d'Auvergne, Viscount Turenne and Duke de Bouillon.

The banks of New-York, their dealers, the clearinghouse, and the panic of 1857 ...

Mode of access: Internet.

Landmarks of English literature /

"The plan adopted in this book has been to deal solely with the very greatest names in the several departments of English literature".--Introd.

The centennial history of the Protestant Episcopal church in the diocese of New York, 1785-1885.

"Prepared for the press by a member of the Committee, under its direction."--Pref.

Chefs-d'œuvre of the industrial arts /

Index, p.387-381.

A new pronouncing dictionary of the Spanish and English languages /

Pt. 2 has t.p. in Spanish.

The silence of Dean Maitland : a novel /

Mode of access: Internet.

Emergency! The dramatic story of the Emergency Service Division of the New York City Police Department.

Mode of access: Internet.

The life of Peter Van Schaack, LL. D. : embracing selections from his correspondence and other writings during the American Revolution, and his exile in England /

Includes errata.