Non-identical twins: Different faces of CR3 and CR4 in myeloid and lymphoid cells of mice and men

Integrins are cell membrane receptors that are involved in essential physiological and serious pathological processes. Their main role is to ensure a closely regulated link between the extracellular matrix and the intracellular cytoskeletal network enabling cells to react to environmental stimuli. Complement receptor type 3 (CR3, alphaMbeta2, CD11b/CD18) and type 4 (CR4, alphaXbeta2, CD11c/CD18) are members of the beta2-integrin family expressed on most white blood cells. Both receptors bind multiple ligands like iC3b, ICAM, fibrinogen or LPS. beta2-integrins are accepted to play important roles in cellular adhesion, migration, phagocytosis, ECM rearrangement and inflammation. Several pathological conditions are linked to the impaired functions of these receptors. CR3 and CR4 are generally thought to mediate overlapping functions in monocytes, macrophages and dendritic cells, therefore the potential distinctive role of these receptors has not been investigated so far in satisfactory details. Lately it has become clear that a functional segregation has evolved between the two receptors regarding phagocytosis, cellular adhesion and podosome formation. In addition to their tasks on myeloid cells, the expression and function of CR3 and CR4 on lymphocytes have also gained interest recently. The picture is further complicated by the fact that while these beta2-integrins are expressed by immune cells both in mice and humans, there are significant differences in their expression level, functions and the pathological consequences of genetic defects. Here we aim to summarize our current knowledge on CR3 and CR4 and highlight the functional differences between these receptors, involving their expression in myeloid and lymphoid cells of both men and mice

Intracardiac hemostasis and fibrinolysis parameters in patients with atrial fibrillation

Aims. To identify intracardiac hemostasis or fibrinolysis abnormalities, which are associated with atrial fibrillation (AF) and increase the risk of thromboembolism. Patients and Methods. Patient group consisted of 24 patients with AF and control group included 14 individuals with other supraventricular tachycardia undergoing transcatheter radiofrequency ablation. Blood samples were drawn from the femoral vein (FV), left atrium (LA), and left atrial appendage (LAA) before the ablation procedure. Fibrinogen, factor VIII (FVIII) and factor XIII activity, von Willebrand factor (VWF) antigen, thrombin-antithrombin (TAT) complex, quantitative fibrin monomer (FM), plasminogen, α2-plasmin inhibitor, plasmin-α2-antiplasmin (PAP) complex, PAI-1 activity, and D-dimer were measured from all samples. Results. Levels of FVIII and VWF were significantly elevated in the FV and LA of AF patients as compared to controls. TAT complex, FM, PAP complex, and D-dimer levels were significantly elevated in the LA as compared to FV samples in case of both groups, indicating a temporary thrombotic risk associated with the catheterization procedure. Conclusions. None of the investigated hemostasis or fibrinolysis parameters showed significant intracardiac alterations in AF patients as compared to non-AF controls. AF patients have elevated FVIII and VWF levels, most likely due to endothelial damage, presenting at both intracardiac and systemic level