5,579 research outputs found
Attachment of the soluble complement regulator factor H to cell and tissue surfaces: relevance for pathology
No full textComplement is a central element of innate immunity and this vital defense system initiates and coordinates immediate immune reactions which attack and eliminate microbes, foreign particles and altered self cells. Newly generated activation products are extremely toxic and consequently, activation is highly restricted in terms of time and space. The initial activation of the alternative complement pathway occurs continuously and the early phase acts indiscriminatoryl and forms on any surface. However, the system discriminates between self and foreign, and therefore allows activation on foreign surfaces e.g. Microbes, and restricts activation on host cells. Consequently, self cells and tissues are protected from the harmful activation products. This protection is mediated by specific regulators or inhibitors, which exist in the fluid phase and/or in membrane-bound forms. Here we review a novel mechanism, i.e. the attachment of the soluble complement regulator factor H to the surface of self cells. This attachment, which is demonstrated experimentally by means of immunofluorescense microscopy and by flow cytometry, increases the inhibitory potential at the cell surface and mediates protection by reducing the local formation of toxic inflammatory products. This attachment is highly relevant and has pathophysiological consequences in several human diseases, including Factor H-associated hemolytic uremic syndrome (FH-HUS), membrano-proliferative glomerulonephritis type II, recurrent microbial infections and chronic inflammation, e.g. rheumatoid arthritis and immune evasion of tumor cells. Defects of this safeguard activity have been recently understood in patients with FH-HUS. Point mutations in the Factor H gene occurring in the C-terminus of the protein result in impaired cell binding capacity of Factor H and, consequently, during an inflammatory insult endothelial cells are not properly protected and are damaged
Attachment of the soluble complement regulator factor H to cell and tissue surfaces: relevance for pathology
No full textComplement is a central element of innate immunity and this vital defense system initiates and coordinates immediate immune reactions which attack and eliminate microbes, foreign particles and altered self cells. Newly generated activation products are extremely toxic and consequently, activation is highly restricted in terms of time and space. The initial activation of the alternative complement pathway occurs continuously and the early phase acts indiscriminatoryl and forms on any surface. However, the system discriminates between self and foreign, and therefore allows activation on foreign surfaces e.g. Microbes, and restricts activation on host cells. Consequently, self cells and tissues are protected from the harmful activation products. This protection is mediated by specific regulators or inhibitors, which exist in the fluid phase and/or in membrane-bound forms. Here we review a novel mechanism, i.e. the attachment of the soluble complement regulator factor H to the surface of self cells. This attachment, which is demonstrated experimentally by means of immunofluorescense microscopy and by flow cytometry, increases the inhibitory potential at the cell surface and mediates protection by reducing the local formation of toxic inflammatory products. This attachment is highly relevant and has pathophysiological consequences in several human diseases, including Factor H-associated hemolytic uremic syndrome (FH-HUS), membrano-proliferative glomerulonephritis type II, recurrent microbial infections and chronic inflammation, e.g. rheumatoid arthritis and immune evasion of tumor cells. Defects of this safeguard activity have been recently understood in patients with FH-HUS. Point mutations in the Factor H gene occurring in the C-terminus of the protein result in impaired cell binding capacity of Factor H and, consequently, during an inflammatory insult endothelial cells are not properly protected and are damaged
The C-terminus of complement factor H is essential for host cell protection
No full textComplement is a powerful self-amplifying system of innate immune defense with the capacity to eliminate microbes directly. Factor H is a central regulator in plasma which protects host tissue from complement mediated damage. Here we characterize the relevance of surface attached factor H, and study the regulatory activity of factor H on endothelial cells. Although these cells expressed membrane bound regulators, cell bound factor H contributed substantially to complement regulatory activity at the cell surface. Blockade of the C-terminus of factor H with monoclonal antibodies inhibited cell binding of this soluble regulator and resulted in enhanced complement activation on the cells. In the absence of factor H, increased deposition and slower inactivation of C3b resulted in higher amount of membrane attack complexes on the cell surface. When the membrane regulators CD55 and CD59 were removed by enzymatic treatment, complement mediated cell lysis was enhanced in the absence of factor H. Importantly, inhibition of the C-terminus did not compromise the regulatory function of factor H in fluid phase. Altogether these data point to a highly relevant, yet so far underestimated role of factor H for complement control at cellular surfaces, and reveal a decisive role of the factor H C-terminus in host cell recognition and protection. (c) 2006 Elsevier Ltd. All rights reserved.NIAID NIH HHS [AI 30040, N01AI30040, R01 AI030040, R01 AI030040-12
Contribution of the infection-associated complement regulator-acquiring surface protein 4 (ErpC) to complement resistance of Borrelia burgdorferi
No full textBorrelia burgdorferi evades complement-mediated killing by interacting with complement regulators through distinct complement regulator-acquiring surface proteins (CRASPs). Here, we extend our analyses to the contribution of CRASP-4 in mediating complement resistance of B. burgdorferi and its interaction with human complement regulators. CRASP-4 (also known as ErpC) was immobilized onto magnetic beads and used to capture proteins from human serum. Following Western blotting, factor H (CFH), CFH-related protein 1 (CFHR1), CFHR2, and CFHR5 were identified as ligands of CRASP-4. To analyze the impact of native CRASP-4 on mediating survival of serum-sensitive cells in human serum, a B. garinii strain was generated that ectopically expresses CRASP-4. CRASP-4-producing bacteria bound CFHR1, CFHR2, and CFHR5 but not CFH. In addition, transformed spirochetes deposited significant amounts of lethal complement components on their surface and were susceptible to human serum, thus indicating that CRASP-4 plays a subordinate role in complement resistance of B. burgdorferi
Joseph Bimeler book order to Peter Kaufmann, February 14, 1845
No full textOrder of two dozen German A.B.C. books (primers) by J.M. Bimeler (by Lewis F. Birk) from Peter Kaufmann.
Led by Joseph Bimeler (sometimes spelled Bäumeler) in 1817, a group of Lutheran separatists left Germany and eventually established the small community of Zoar in Tuscarawas County, Ohio. The group formed the Society of Separatists of Zoar, in which each person donated his or her property to the community as a whole, and in exchange for their work, the society would provide for them. After decades of economic prosperity, the unity of the village declined, and by 1898 the Zoarites disbanded the society.
Peter Kaufmann was a German immigrant and intellectual. He arrived first in Philadelphia, Pennsylvania, in 1820; in 1826 he became professor of languages at the Harmony Society town of Economy, Pennsylvania. In 1827, Kaufmann led the establishment of Teutonia, a utopian community in Columbiana County, Ohio, and published its weekly titled "Teutonia: The Herald of a Better Time." Following this he moved to Canton, Ohio, where he became translator and editor of "Der Vaterlandsfreund und Geist der Zeit" under Solomon Sala. Additionally, Kaufmann wrote a number of books on education, as well as a German almanac. He was also an influential Democrat, counting President Van Buren among his friends, and knew Ralph Waldo Emerson
Anti-factor H autoantibodies block C-terminal recognition function of factor H in hemolytic uremic syndrome
No full textThe atypical form of the kidney disease hemolytic uremic syndrome (aHUS) is associated with defective complement regulation. In addition to mutations in complement regulators, factor H (FH)specific autoantibodies have been reported for aHUS patients. The aim of the present study was to understand the role of these autoantibodies in aHUS. First, the binding sites of FH autoantibodies from 5 unrelated aHUS patients were mapped using recombinant FH fragments and competitor antibodies. For all 5 autoantibodies, the binding site was localized to the FH C-terminus. In a functional assay, isolated patient IgG inhibited FH binding to C3b. In addition, autoantibody positive patients' plasma caused enhanced hemolysis of sheep erythrocytes, which was reversed by adding FH in excess. These results suggest that aHUS associated FH autoantibodies mimic the effect of C-terminal FH mutations, as they inhibit the regulatory function of FH at cell surfaces by blocking its C-terminal recognition region
Composting of aged reed bed biosolids for beneficial reuse: a case study in New Jersey, USA
No full textReed beds with Phragmites australis (common reed) have been utilized to decrease the water, nutrient and volatile solids content of sewage sludge. An efficient disposal/reuse option was sought for reed bed biosolids accumulated over a 15 year period at a wastewater treatment facility in New Jersey, USA. The study facility had 14 reed beds, each with 1000 wet tons capacity, which were full, and so the solids needed to be removed. Because P. australis is considered an invasive species in New Jersey and several other states in the United States, disposal or reuse of solids containing this plant is regulated. Composting was examined as a potential treatment for destroying the plant’s reproductive rhizomes. The high temperatures achieved during composting were also tested to determine if regulatory criteria for pathogen reduction could be met, making the composted product suitable for unrestricted land application. Preliminary studies indicated the sludge had stabilized to the point where self-heating did not occur. Among the carbon amendments tested in the laboratory to stimulate compositing activity, Phragmites above ground biomass was determined to be most suitable. In a field test, Phragmites above ground biomass was mixed with reed bed biosolids at a 1:2 (w/w) ratio. The temperatures achieved resulted in complete mortality of Phragmites rhizomes. In laboratory tests, rhizomes placed in a drying oven at 50ºC for 24 hours, or 55ºC for 12 hours, showed 100% plant mortality. However, under field conditions pile temperatures could not be maintained long enough for the sludge to meet the USEPA 503 biosolids time-temperature pathogen rule requirements for unrestricted land application, even though sample fecal coliform counts did meet regulatory limits.Peer reviewed
Anti-factor H autoantibodies and hemolytic uremic syndrome: role of the C-terminus of factor H for activity on endothelial cells
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