Renal disease associated with inherited disorders of the complement system.

The human complement system is vital for host defense and plays a role in a number of inflammatory disorders. Inherited deficiency or dysfunction of most of the individual complement components occurs uncommonly. The phenotype displayed by such patients varies with the specific component deficiency and ranges from recurrent infections to autoimmune diseases.

Immune complex glomerulonephritis following bone marrow transplantation in C3 deficient mice.

Background: The role of circulating complement in host defense and immune disease is well established. Although a number of cells and tissues are capable of synthesizing complement components locally, the importance of such local synthesis in immune disease has been difficult to establish.

Methodology/principal Findings: We used bone marrow transplantation (BMT) between C3 knockout (C3KO) and wild type (WT) mice to construct animals that were discordant for systemic (hepatic) and local (monocytic) C3 synthetic capacity.

Conserved ETS domain arginines mediate DNA binding, nuclear localization, and a novel mode of bZIP interaction.

The DNA-binding ETS transcription factor Spi-1/PU.1 is of central importance in determining the myeloid-erythroid developmental switch and is required for monocyte and osteoclast differentiation. Many monocyte genes are dependent upon this factor, including the gene that codes for interleukin-1beta.

Nonparathyroid hormone-mediated calcium resorption in a rat model of immune glomerulonephritis.

Skeletal demineralization is a frequent accompaniment of chronic renal disease and is likely multifactorial. We studied the role of inflammation in stimulating bone resorption in a rat model of glomerulonephritis (GN). Three-week-old Sprague-Dawley rats received either saline (n = 8) or horse spleen apoferritin and lipopolysaccharide (HSA/LPS, n = 8) by intraperitoneal injection, for 6 weeks; afterward, they were observed for either an additional 3 weeks (9 weeks total; n = 4 from each group) or 14 weeks (20 weeks total; n = 4 from each group).

C3 is central to the interstitial component of experimental immune complex glomerulonephritis.

We have suggested that renal tubular synthesis of C3 and its activation in the cortical interstitium is a mechanism for the progression of glomerulonephritis to interstitial injury. To test this hypothesis, immune complex glomerulonephritis was induced in C57BL/6 mice by intraperitoneal injections of horse spleen apoferritin and lipopolysaccharide (HSA/LPS). When compared to wild-type (WT) animals, C3 knockout (C3KO) mice had glomerular changes that were identical.

Heparin modulates integrin-mediated cellular adhesion: specificity of interactions with alpha and beta integrin subunits.

Heparin is known to influence the growth, proliferation, and migration of vascular cells, but the precise mechanisms are unknown. We previously demonstrated that unfractionated heparin (UH) binds to the platelet integrin alpha(IIb)beta(3), and enhances ligand binding. To help define the specificity and site(s) of heparin-integrin interactions, we employed the erythroleukemic K562 cell line, transfected to express specific integrins (alpha(v)beta(3), alpha(v)beta(5), and alpha(IIb)beta(3)).

Discovery of novel benzothiazolesulfonamides as potent inhibitors of HIV-1 protease.

The human immunodeficiency virus (HIV) has been shown to be the causative agent for AIDS. The HIV virus encodes for a unique aspartyl protease that is essential for the production of enzymes and proteins in the final stages of maturation. Protease inhibitors have been useful in combating the disease.