Jean-Eric Alard

Université de Bretagne Occidentale | UBO · EA2216 - Immunologie et Pathologie

Protein-protein interactions (PPIs) are receiving increasing interest, much sparked by the realization they represent druggable targets. Recently, we successfully developed a peptidic inhibitor, RRYGTSKYQ ("SKY" peptide), that shows high potential in vitro and in vivo to interrupt a PPI between the platelet-borne chemokine CCL5 and the neutrophil-d...

In acute and chronic inflammation, neutrophils and platelets, both of which promote monocyte recruitment, are often activated simultaneously. We investigated how secretory products of neutrophils and platelets synergize to enhance the recruitment of monocytes. We found that neutrophil-borne human neutrophil peptide 1 (HNP1, α-defensin) and platelet...

Heat shock proteins (HSPs) are a wide family of molecular chaperones. The first members of HSPs were observed in cellular stress reactions, especially in thermic changes ascribing their generic names. HSPs can be induced not only following temperature shift but also after other stress pressures such as shear force, cellular injury, and heavy metal...

Rationale: The leukocyte response in acute inflammation is characterized by an initial recruitment of neutrophils preceding a second wave of monocytes. Neutrophil-derived granule proteins were suggested to hold an important role in this cellular switch. The exact mechanisms by which neutrophils mediate these processes are only partially understood...

Acute lung injury (ALI) causes high mortality, but its molecular mechanisms and therapeutic options remain ill-defined. Gram-negative bacterial infections are the main cause of ALI, leading to lung neutrophil infiltration, permeability increases, deterioration of gas exchange, and lung damage. Platelets are activated during ALI, but insights into t...

Heat shock protein (hsp) 60 that provides "danger signal" binds to the surface of resting endothelial cells (EC) but its receptor has not yet been characterized. In mitochondria, hsp60 specifically associates with adenosine triphosphate (ATP) synthase. We therefore examined the possible interaction between hsp60 and ATP synthase on EC surface. Usin...

During the antiphospholipid syndrome, beta2-gpI interacts with phospholipids on endothelial cell (EC) surface to allow the binding of autoantibodies. However, induced-pathogenic intracellular signals suggest that beta2-gpI associates also with a receptor that is still not clearly identified. TLR2 and TLR4 have long been suspected, yet interactions...

Heat shock protein (HSP) 60, up-regulated by endothelial cells (ECs) to resist stress, is the target of a subgroup of apoptosis-inducing anti-EC autoantibodies (Abs) in human vasculitides. Given that HSP60 is not a transmembrane protein, the mechanism by which these auto-Abs induces apoptosis is unclear. EC membrane proteins were analyzed using bid...

Anti-endothelial cell (EC) antibodies (AECA) are a heterogeneous group of antibodies directed against a variety of EC membrane proteins. A pathogenic role for AECA in diseases that involve the vascular system has not been clearly demonstrated. Induction of EC apoptosis appears to be one of the mechanisms by which AECA may exert their effect. AECA f...

Clinical and pathological manifestations present as heterogeneous in vasculitides. Thus, inflammation can affect arteries, arterioles, capillaries, venules, and veins toward major body regions. One common feature of vascular diseases appears to be the presence of anti-HSP60 autoantibodies arising either consecutively to infection and molecular mimi...

Heat-shock protein (Hsp) family is made up of heterogeneous proteins of which Hsp60 members are the most studied. It is now generally admitted that Hsp60 is not only a mitochondrial component but can be localized on the membrane cell surface. Considered as a signal danger following infections, Hsp60 can induce the production of anti-Hsp60 antibodie...

Anti-endothelial cell antibodies (AECAs), which recognize a number of endothelial antigens, are seen in patients with systemic autoimmune diseases, more often in the presence of vasculitis than in its absence. Some AECAs induce apoptosis of endothelial cells (ECs), but their target antigens remain unknown. The aim of this study was to determine whe...