Factor H (FH) is a member of the regulators of complement activation family and is a complement control protein. It is a large (155 kilodaltons), soluble glycoprotein that circulates in human plasma (at typical concentrations of 200–300 micrograms per milliliter[5][6][7]). Its principal function is to regulate the alternative pathway of the complement system, ensuring that the complement system is directed towards pathogens 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 Factor I–mediated C3b cleavage, and decay accelerating activity against the alternative pathway C3-convertase, C3bBb. Factor H exerts its protective action on self cells and self surfaces but not on the surfaces of bacteria or viruses. There are however, important exceptions, such as for example the bacterial pathogen, Neisseria meningitidis (also called the meningococcus). This human pathogen has evolved mechanisms to recruit human FH and down-regulate the alternative pathway.[8] Binding of FH permits the bacteria to proliferate in the bloodstream and cause disease.[9]
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.[10] 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 glycosaminoglycans (GAGs) and or sialic acids 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.[11][12]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Sofat R, Mangione PP, Gallimore JR, Hakobyan S, Hughes TR, Shah T, et al. (April 2013). "Distribution and determinants of circulating complement factor H concentration determined by a high-throughput immunonephelometric assay". Journal of Immunological Methods. 390 (1–2): 63–73. doi:10.1016/j.jim.2013.01.009. PMID23376722.
^Pangburn MK (August 2000). "Host recognition and target differentiation by factor H, a regulator of the alternative pathway of complement". Immunopharmacology. 49 (1–2): 149–157. doi:10.1016/S0162-3109(00)80300-8. PMID10904114.
^Rodríguez de Córdoba S, Esparza-Gordillo J, Goicoechea de Jorge E, Lopez-Trascasa M, Sánchez-Corral P (June 2004). "The human complement factor H: functional roles, genetic variations and disease associations". Molecular Immunology. 41 (4): 355–367. doi:10.1016/j.molimm.2004.02.005. PMID15163532.
