Paper Chase is a research database designed to offer abstracts of research articles published in journals that have a highly rated impact factor as determined by ISI Impact Factor and PageRank. Abstracts are organized by date, with the most recently published papers listed first. 

Paper Chase

A ligand-specific blockade of the integrin Mac-1 selectively targets pathologic inflammation while maintaining protective host-defense.

Nat Commun. 02 06, 2018;9(1):525.
Wolf D, Anto-Michel N, Blankenbach H, Wiedemann A, Buscher K, Hohmann JD, Lim B, Bäuml M, Marki A, Mauler M, Duerschmied D, Fan Z, Winkels H, Sidler D, Diehl P, Zajonc DM, Hilgendorf I, Stachon P, Marchini T, Willecke F, Schell M, Sommer B, von Zur Muhlen C, Reinöhl J, Gerhardt T, Plow EF, Yakubenko V, Libby P, Bode C, Ley K, Peter K, Zirlik A.

Cardiology and Angiology I, University Heart Center, and Medical Faculty, University of Freiburg, Freiburg, 79106, Germany.

Abstract:

Integrin-based therapeutics have garnered considerable interest in the medical treatment of inflammation. Integrins mediate the fast recruitment of monocytes and neutrophils to the site of inflammation, but are also required for host defense, limiting their therapeutic use. Here, we report a novel monoclonal antibody, anti-M7, that specifically blocks the interaction of the integrin Mac-1 with its pro-inflammatory ligand CD40L, while not interfering with alternative ligands. Anti-M7 selectively reduces leukocyte recruitment in vitro and in vivo. In contrast, conventional anti-Mac-1 therapy is not specific and blocks a broad repertoire of integrin functionality, inhibits phagocytosis, promotes apoptosis, and fuels a cytokine storm in vivo. Whereas conventional anti-integrin therapy potentiates bacterial sepsis, bacteremia, and mortality, a ligand-specific intervention with anti-M7 is protective. These findings deepen our understanding of ligand-specific integrin functions and open a path for a new field of ligand-targeted anti-integrin therapy to prevent inflammatory conditions.

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