Lupus FAQ » Lupus Erythematosus » complement

complement

Question:

This comes from the Explore site. If one knows a little about lots .. then one can look at this .. and say .. well hell .. Dr. Shute pronounced a tocopherol regimen to be a CURE for this very problem. So would tocopherol or lack thereof BE .. ‘linked’ here? Somewhat like a lack of vitamin C/ascorbate is linked to porphyria? Since porphyria does not manifest UNTIL there is excess iron in the body .. and iron is KNOWN to deplete destroy vitamin C and vitamin E/tocopherol .. then the fact porphyria is linked to iron .. and linked to MS .. then could it BE .. the iron which destroys vitamin E which leads to a lack of E to produce the factors required to PREVENT the body from ‘turning on itself’ .. ?                        Solving the Pregnancy Paradox             Researchers have found proteins that play a key role          in protecting an embryo from its mother’s immune system–                    and that may one day help treat women                      who suffer multiple miscarriages.    The Complement System    Antibodies (blue) attach to antigens (red) on an invading cell’s    membrane (gray), attracting a series of complement proteins (purple)    (top two frames). A membrane attack complex opens a lesion, through    which water rushes in and bursts the cell (bottom two frames).                complement Image: The University of Wisconsin                            MORE EXPLORE FEATURES    Pregnancy has long presented scientists with a paradox: A mother’s    immune system should attack any foreign tissue, and her developing    child is just that–because it bears some of its father’s genetic    material. So why don’t all pregnancies end in miscarriage, just as    many organ transplants ultimately meet with rejection?                                            normal Image: Hector D. Molina      NORMAL EMBRYO. A nine-day-old mouse embryo, which produces a protein          (Crry), develops without damage inflicted by its mother’s immune                                                                   system.    In searching for a resolution, immunologists have sought out factors    that might somehow suppress a mother’s so-called acquired immunity,    which sics T and B cells on "non-self" invaders, like a baby. But this    form of immunity is only one of several cooperating systems. And it    now seems that scientists have been looking in the wrong place.    Hector D. Molina and his colleagues at Washington University in St.    Louis recently discovered that factors controlling innate immunity–an    evolutionarily older and more primative arsenal than our acquired    defenses–are essential for maintaining normal pregnancies in mice.    They reported their work in the January 20th issue of Science.    Molina wasn’t trying to tackle the pregnancy paradox when he started    his work. Instead he was hoping to learn whether the murine gene,    complement receptor-related gene Y (Crry), and its product Crry,    helped protect the body from damage inflicted by inflammation. The    swollen, hot, red splotches inflammation causes on the outside of the    body speak of a cellular hell on the inside, where sundry immune cells    attack and destroy infected or foreign tissues in a variety of ways.    One crucial tactic involves complement proteins that parachute down to    foreign cells and, through a series of steps, tag them for destruction    or eventually blast fatal holes through their membranes. Crry acts to    prevent two complement proteins, C3 and C4, from marking foreign cells    early on in the cycle.                                          abnormal Image: Hector D. Molina    ABNORMAL EMBRYO. A nine-day-old mouse embryo, which lacks a protective          protein (Crry), is being attacked by its mother’s immune system.    Molina planned to further elucidate Crry’s function in vivo by    creating Crry knockout mice. He disrupted the genes in one group of    animals and crossed them with healthy animals to form a generation of    mice having one normal and one mutant copy of Crry. The group expected    that at least a quarter of the offpring from these mice would inherit    two mutant copies of Crry and so have no Crry protein regulation of C3    or C4.    Instead they found no Crry deficiency among the 245 births in their    study. All of the animals inheriting two mutant copies of Crry had in    fact died as embryos some 10 days after conception. Although Crry is    not the only complement regulator, it appeared as though its absence    was enough to leave an embryo vulnerable to its mother’s complement    system. Normal animals, they found, did express early on large amounts    of Crry on fetal cells called trophoblasts–which help form the    boundary between mother and child.    To shore up the argument, Molina also created mice that lacked both    Crry and complement proteins. These animals gave birth to    Crry-deficient but otherwise healthy pups–further proving that Crry    served to protect normal developing embryos from their mother’s    immunity. No complement, no danger. "It appears that the mother has to    constantly control complement activation, especially on the surface of    the placenta, for an embryo to survive," Molina notes.    Crry exists only in rodents, but two substances–decay accelerating    factor (DAF) and membrane cofactor protein (MCP)–serve a like purpose    in people. And it is possible that DAF and MCP deficiencies might play    a role in miscarriages. Molina’s team plans to test this idea next,    focusing on women who have suffered multiple miscarriage or have    autoimmune diseases such as lupus erythematosus. "Using the mouse    studies as a framework," Molina adds, "we can jump to human studies    and see whether miscarriages in women also involve complement    regulation." If they do, therapies to help certain women carry to term    may not be far off.    –Kristin Leutwyler      _________________________________________________________________    RELATED LINKS:    The Complement System, from the University of Wisconsin’s Why Files    Complement Review, from the Integrated Medical Curriculum Homepage      _________________________________________________________________ Who loves ya. Tom — Jesus was a Vegetarian! http://www.nucleus.com/watchman Moses was a Mystic! http://www.nucleus.com/watchman/light.html

Response:

watchman <watch…@nucleus.com> wrote: > This comes from the Explore site. > If one knows a little about lots .. then one can look at this .. and say > .. well hell .. Dr. Shute pronounced a tocopherol regimen to be a CURE for > this very problem. > So would tocopherol or lack thereof BE .. ‘linked’ here?

Looks like Dr. Shute was right .. fifty years ago .. Trophoblast .. Gotta love Medline ..    J Biol Chem 2001 Jan 19;276(3):1669-72 Alpha-tocopherol transfer protein is important for the normal development of placental labyrinthine trophoblasts in mice.     Jishage K, Arita M, Igarashi K, Iwata T, Watanabe M, Ogawa M, Ueda O,     Kamada N, Inoue K, Arai H, Suzuki H    Pharmaceutical Technology Laboratory, Chugai Pharmaceutical Co., Ltd.,    1-135 Komakado, Gotemba, Shizuoka, 412-8513 Japan.    Alpha-tocopherol transfer protein (alpha-TTP), a cytosolic protein    that specifically binds alpha-tocopherol, is known as a product of the    causative gene in patients with ataxia that is associated with vitamin    E deficiency. Targeted disruption of the alpha-TTP gene revealed that    alpha-tocopherol concentration in the circulation was regulated by    alpha-TTP expression levels. Male alpha-TTP(-/-) mice were fertile;    however, placentas of pregnant alpha-TTP(-/-) females were severely    impaired with marked reduction of labyrinthine trophoblasts, and the    embryos died at mid-gestation even when fertilized eggs of    alpha-TTP(+/+) mice were transferred into alpha-TTP(-/-) recipients.    The use of excess alpha-tocopherol or a synthetic antioxidant (BO-653)    dietary supplement by alpha-TTP(-/-) females prevented placental    failure and allowed full-term pregnancies. In alpha-TTP(+/+) animals,    alpha-TTP gene expression was observed in the uterus, and its level    transiently increased after implantation (4.5 days postcoitum). Our    results suggest that oxidative stress in the labyrinth region of the    placenta is protected by vitamin E during development and that in    addition to the hepatic alpha-TTP, which governs plasma    alpha-tocopherol level, the uterine alpha-TTP may also play an    important role in supplying this vitamin.    PMID: 11076932, UI: 21125713      _________________________________________________________________    Save the above report in [Macintosh] [Text] format    Order documents on this page through Loansome Doc      _________________________________________________________________ – Hide quoted text — Show quoted text -> Somewhat like a lack of vitamin C/ascorbate is linked to porphyria? > Since porphyria does not manifest UNTIL there is excess iron in the body > .. and iron is KNOWN to deplete destroy vitamin C and vitamin E/tocopherol > .. then the fact porphyria is linked to iron .. and linked to MS .. then > could it BE .. the iron which destroys vitamin E which leads to a lack of > E to produce the factors required to PREVENT the body from ‘turning on > itself’ .. ? >                        Solving the Pregnancy Paradox >             Researchers have found proteins that play a key role >          in protecting an embryo from its mother’s immune system– >                    and that may one day help treat women >                      who suffer multiple miscarriages. >    The Complement System >    Antibodies (blue) attach to antigens (red) on an invading cell’s >    membrane (gray), attracting a series of complement proteins (purple) >    (top two frames). A membrane attack complex opens a lesion, through >    which water rushes in and bursts the cell (bottom two frames). >                complement Image: The University of Wisconsin >                            MORE EXPLORE FEATURES >    Pregnancy has long presented scientists with a paradox: A mother’s >    immune system should attack any foreign tissue, and her developing >    child is just that–because it bears some of its father’s genetic >    material. So why don’t all pregnancies end in miscarriage, just as >    many organ transplants ultimately meet with rejection? >                                            normal Image: Hector D. Molina >      NORMAL EMBRYO. A nine-day-old mouse embryo, which produces a protein >          (Crry), develops without damage inflicted by its mother’s immune >                                                                   system. >    In searching for a resolution, immunologists have sought out factors >    that might somehow suppress a mother’s so-called acquired immunity, >    which sics T and B cells on "non-self" invaders, like a baby. But this >    form of immunity is only one of several cooperating systems. And it >    now seems that scientists have been looking in the wrong place. >    Hector D. Molina and his colleagues at Washington University in St. >    Louis recently discovered that factors controlling innate immunity–an >    evolutionarily older and more primative arsenal than our acquired >    defenses–are essential for maintaining normal pregnancies in mice. >    They reported their work in the January 20th issue of Science. >    Molina wasn’t trying to tackle the pregnancy paradox when he started >    his work. Instead he was hoping to learn whether the murine gene, >    complement receptor-related gene Y (Crry), and its product Crry, >    helped protect the body from damage inflicted by inflammation. The >    swollen, hot, red splotches inflammation causes on the outside of the >    body speak of a cellular hell on the inside, where sundry immune cells >    attack and destroy infected or foreign tissues in a variety of ways. >    One crucial tactic involves complement proteins that parachute down to >    foreign cells and, through a series of steps, tag them for destruction >    or eventually blast fatal holes through their membranes. Crry acts to >    prevent two complement proteins, C3 and C4, from marking foreign cells >    early on in the cycle. >                                          abnormal Image: Hector D. Molina >    ABNORMAL EMBRYO. A nine-day-old mouse embryo, which lacks a protective >          protein (Crry), is being attacked by its mother’s immune system. >    Molina planned to further elucidate Crry’s function in vivo by >    creating Crry knockout mice. He disrupted the genes in one group of >    animals and crossed them with healthy animals to form a generation of >    mice having one normal and one mutant copy of Crry. The group expected >    that at least a quarter of the offpring from these mice would inherit >    two mutant copies of Crry and so have no Crry protein regulation of C3 >    or C4. >    Instead they found no Crry deficiency among the 245 births in their >    study. All of the animals inheriting two mutant copies of Crry had in >    fact died as embryos some 10 days after conception. Although Crry is >    not the only complement regulator, it appeared as though its absence >    was enough to leave an embryo vulnerable to its mother’s complement >    system. Normal animals, they found, did express early on large amounts >    of Crry on fetal cells called trophoblasts–which help form the >    boundary between mother and child. >    To shore up the argument, Molina also created mice that lacked both >    Crry and complement proteins. These animals gave birth to >    Crry-deficient but otherwise healthy pups–further proving that Crry >    served to protect normal developing embryos from their mother’s >    immunity. No complement, no danger. "It appears that the mother has to >    constantly control complement activation, especially on the surface of >    the placenta, for an embryo to survive," Molina notes. >    Crry exists only in rodents, but two substances–decay accelerating >    factor (DAF) and membrane cofactor protein (MCP)–serve a like purpose >    in people. And it is possible that DAF and MCP deficiencies might play >    a role in miscarriages. Molina’s team plans to test this idea next, >    focusing on women who have suffered multiple miscarriage or have >    autoimmune diseases such as lupus erythematosus. "Using the mouse >    studies as a framework," Molina adds, "we can jump to human studies >    and see whether miscarriages in women also involve complement >    regulation." If they do, therapies to help certain women carry to term >    may not be far off. >    –Kristin Leutwyler >      _________________________________________________________________ >    RELATED LINKS: >    The Complement System, from the University of Wisconsin’s Why Files >    Complement Review, from the Integrated Medical Curriculum Homepage >      _________________________________________________________________ > Who loves ya. > Tom > — > Jesus was a Vegetarian! http://www.nucleus.com/watchman > Moses was a Mystic! http://www.nucleus.com/watchman/light.html

– Jesus was a Vegetarian! http://www.nucleus.com/watchman Moses was a Mystic! http://www.nucleus.com/watchman/light.html

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