An Activation-Specific Anti-Mac-1 Designed-Ankyrin-Repeat-Protein Attenuates Colitis in Mice.

(1) Background: Inflammatory bowel diseases are complex and multifactorial disorders of unknown etiology. The extravasation of activated leukocytes is a critical step in the pathogenesis of these diseases. Leukocyte integrin Mac-1 (αβ; CD11b/CD18) is crucial for the extravasation of myeloid cells, and a novel activation-specific anti-Mac-1 Designed Ankyrin Repeat protein (DARPin F7) is a promising therapeutic agent for inflammatory diseases.

Decreased level of serum NT-proCNP associates with disease severity in COVID-19.

Background: C-type natriuretic peptide (CNP) is an endothelium-derived paracrine molecule with an important role in vascular homeostasis. In septic patients, the serum level of the amino-terminal propeptide of CNP (NT-proCNP) shows a strong positive correlation with inflammatory biomarkers and, if elevated, correlates with disease severity and indicates a poor outcome. It is not yet known whether NT-proCNP also correlates with the clinical outcome of patients suffering from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

An activation specific anti-Mac-1 designed ankyrin repeat protein improves survival in a mouse model of acute lung injury.

The acute respiratory distress syndrome (ARDS) is a life-threatening clinical condition. The number of ARDS cases has risen dramatically recently but specific treatment options are limited. ARDS is associated with an overshooting inflammatory response and neutrophils play a central role in its pathogenesis.

Early platelet dysfunction in patients receiving extracorporeal membrane oxygenation is associated with mortality.

Extracorporeal membrane oxygenation (ECMO) is used for patients with cardiopulmonary failure and is associated with severe bleeding and poor outcome. Platelet dysfunction may be a contributing factor. The aim of this prospective observational study was to characterize platelet dysfunction and its relation to outcome in ECMO patients.

Monocyte Dysfunction Detected by the Designed Ankyrin Repeat Protein F7 Predicts Mortality in Patients Receiving Veno-Arterial Extracorporeal Membrane Oxygenation.

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is used for critically ill patients requiring hemodynamic support but has been shown to induce an inflammatory response syndrome potentially leading to severe complications and poor outcome. Monocytes are comprised of different subsets and play a central role in the innate immune system. The small binding proteins, Designed Ankyrin Repeat Protein "F7" and single chain variable fragment "MAN-1," specifically detect the activated conformation of the leukocyte integrin Mac-1 enabling the highly sensitive detection of monocyte activation status.

A DARPin targeting activated Mac-1 is a novel diagnostic tool and potential anti-inflammatory agent in myocarditis, sepsis and myocardial infarction.

The monocyte β-integrin Mac-1 is crucial for leukocyte-endothelium interaction, rendering it an attractive therapeutic target for acute and chronic inflammation. Using phage display, a Designed-Ankyrin-Repeat-Protein (DARPin) was selected as a novel binding protein targeting and blocking the α I-domain, an activation-specific epitope of Mac-1. This DARPin, named F7, specifically binds to activated Mac-1 on mouse and human monocytes as determined by flow cytometry.

Annexin V positive microvesicles are elevated and correlate with flow rate in patients receiving veno-arterial extracorporeal membrane oxygenation.

Objectives: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is used in critically ill patients requiring haemodynamic support. Microvesicles (MV) are released by activated blood cells acting as mediators of intercellular communication. We aimed to determine MV count and composition over time in patients with VA-ECMO and explore what drives MV formation.

Molecular magnetic resonance imaging of activated platelets allows noninvasive detection of early myocarditis in mice.

MRI sensitivity for diagnosis and localization of early myocarditis is limited, although it is of central clinical interest. The aim of this project was to test a contrast agent targeting activated platelets consisting of microparticles of iron oxide (MPIO) conjugated to a single-chain antibody directed against ligand-induced binding sites (LIBS) of activated glycoprotein IIb/IIIa (= LIBS-MPIO). Myocarditis was induced by subcutaneous injection of an emulsion of porcine cardiac myosin and complete Freund's adjuvant in mice.

Cardiomyocyte microvesicles: proinflammatory mediators after myocardial ischemia?

Myocardial infarction is a frequent complication of cardiovascular disease leading to high morbidity and mortality worldwide. Elevated C-reactive protein (CRP) levels after myocardial infarction are associated with heart failure and poor prognosis. Cardiomyocyte microvesicles (CMV) are released during hypoxic conditions and can act as mediators of intercellular communication.