Factor H

Factor H (FH) is a member of the regulators of complement activation family and is a <a href="/facts/Complement_control_protein/LJceJgzW">complement control protein</a>. It is a large (155 kilodaltons), soluble <a href="/facts/Glycoprotein/bKPzzW7m">glycoprotein</a> that circulates in human <a href="/facts/Blood_plasma/oHuwwugG">plasma</a> (at typical concentrations of 200–300 <a href="/facts/Micrograms/aAHxytph">micrograms</a> per <a href="/facts/Milliliter/QKwbQz8I">milliliter</a>). Its principal function is to regulate the <a href="/facts/Alternative_Pathway/eN5PARpC">alternative pathway</a> of the <a href="/facts/Complement_system/vRSrQDUv">complement system</a>, ensuring that the complement system is directed towards <a href="/facts/Pathogens/axMXtV1M">pathogens</a> or other dangerous material and does not damage host tissue. Factor H regulates complement activation on self cells and surfaces by possessing both cofactor activity for <a href="/facts/Complement_Factor_I/V9lHyyRn">Factor I</a>–mediated <a href="/facts/C3b/gQ2bfe0R">C3b</a> cleavage, and decay accelerating activity against the alternative pathway <a href="/facts/C3-convertase/yCSPm074">C3-convertase</a>, C3bBb. Factor H exerts its protective action on self cells and self surfaces but not on the surfaces of <a href="/facts/Bacteria/wC8xSCsU">bacteria</a> or <a href="/facts/Viruses/mf88Bcbl">viruses</a>. There are however, important exceptions, such as for example the bacterial pathogen, <a href="/facts/Neisseria_meningitidis/u4SqwHuc">Neisseria meningitidis</a> (also called the meningococcus). This human pathogen has evolved mechanisms to recruit human FH and down-regulate the alternative pathway. Binding of FH permits the bacteria to proliferate in the bloodstream and cause disease.
The ability of Factor H to exert its protective action on self cells and self surfaces is thought to be the result of Factor H having the ability to adopt conformations with lower or higher activities as a cofactor for C3 cleavage or decay accelerating activity. The lower activity conformation is the predominant form in solution and is sufficient to control fluid phase amplification. The more active conformation is thought to be induced when Factor H binds to <a href="/facts/Glycosaminoglycans/fo22ktAQ">glycosaminoglycans</a> (GAGs) and or <a href="/facts/Sialic_acid/spYNJFbh">sialic acids</a> that are generally present on host cells but not, normally, on pathogen surfaces ensuring that self surfaces are protected whilst complement fixation proceeds unabated on foreign surfaces.

Factor H open-in-new

Factor H