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Biomedical subjects

Lea Ziporen

Publications and source records attributed to Lea Ziporen.

2 recordsLinked to original sources

Cell signals transduced by complement.

The complement system is composed of soluble blood plasma proteins and cell membrane proteins. A major function of the soluble complement proteins is to bind to and destroy invading pathogens. The membrane proteins of the complement system are divided into complement receptors and complement regulatory proteins. Complement receptors on phagocytic cells promote binding and engulfment of pathogens coated with complement opsonins, whereas complement regulatory proteins protect healthy tissues from accidental damage by the soluble complement proteins. Upon binding of complement proteins or protein fragments that are generated during complement activation, these receptors and regulatory proteins transduce various signals into cells bearing them. The complement membrane attack complex C5b-9 binds to cell membranes, independent of any receptor, and also activates multiple signaling pathways. The receptor-dependent and -independent signals transduced by complement components are of great consequence to health and disease. Complement plays an important role in immunoregulation by activating B and T lymphocytes. It may also exert pro- or anti-apoptotic effects on various cell types. At sublytic doses, the complement membrane attack complex has wide-range effects on many cell types leading to cellular responses, such as secretion, adherence, aggregation, chemotaxis and even cell division. Sublytic complement also induces increased cell resistance to lytic doses of complement. Finally, certain pathogens take advantage of complement membrane proteins to gain entry into cells. The emerging data on these complement-related signaling pathways is hereby described.

Animals↗

Neurological dysfunction associated with antiphospholipid syndrome: histopathological brain findings of thrombotic changes in a mouse model.

The aim of this work was to study the pathological processes underlying neurological dysfunctions displayed by BALB/C mice induced with experimental antiphospholipid syndrome (APS), as we have previously reported. Experimental APS was induced in female BALB/C mice by immunization with a pathogenic monoclonal anticardiolipin (aCL) antibody, H-3 (n = 10), or an irrelevant immunoglobulin in controls (n = 10). Mice immunized with H-3 developed clinical and neurological manifestations of APS, including: embryo resorption, thrombocytopenia neurological defects and behavioral disturbances. In mouse sera, the titer of various autoantibodies were elevated, including: anti-phospholipids (aPLs), anti-beta2 glycoprotein-I (beta2GPI), anti-endothelial cell antibodies (AECA) and low titer of anti-dsDNA antibodies. Five months after APS induction, mice were sacrificed and brain tissue specimens were processed for hematoxylin and eosin (H&E), immunofluorescence staining and transmission electron microscopy (TEM). H&E staining of cortical tissue derived from all APS mice revealed mild inflammation, localized mainly in the meninges. Prominent IgG deposits in the large vessel walls and perivascular IgG leakage were observed by immunofluorescence. No large thrombi were observed in large vessels. However, EM evaluation of cerebral tissue revealed pathological changes in the microvessels. Thrombotic occlusion of capillaries in combination with mild inflammation was the main finding and may underlie the neurological defects displayed by mice with APS.

Animals↗