For example, activation of factor B releases Bb, a serine protease and key component of the alternative pathway C3 and C5 convertases, and Ba, a small polypeptide composed of three shushi domains with no known biological function. sMAC: A Unique Activation FragmentĪctivation of complement liberates more functional polypeptide fragments of various molecular species than any other immunological or hematological pathway.
#Smac registration key series#
Additional non-canonical roles of complement are discussed in a series published in Seminars in Immunology ( 23).
#Smac registration key Activator#
These activities are tightly controlled by more than a dozen fluid-phase and membrane-bound regulatory molecules whose function is to keep complement activation in proportion to the amount of activator present and to limit damage to host tissues ( 1, 21, 22). Effector functions mediated by complement are driven by the proteolytic generation of activation fragments that either 1) bind to receptors expressed on both immune and non-immune cells, or 2) covalently attach to cell surfaces adjacent to sites of complement activation ( 1– 3). Complement also serves to help in controlling T and B cell activation and function, stem cells and developmental processes, modulate basic cellular processes in intracellular sensing and cellular metabolism as it relates to immune responses ( 7– 15), synaptic pruning ( 16, 17), modulation of the circadian clock ( 18), and possible contributions to schizophrenia ( 19, 20). Complement-mediated immune effector functions include chemoattraction of immune cells, activation of leukocytes, platelets and essentially all cell types proximal to complement activation, opsonization of invading pathogens, enhancement of the acute-phase response, lysis of susceptible pathogens and modulation of lymphocyte-mediated immune responses ( 1, 2, 4– 6). Composed of ~50 proteins, four activation pathways (classical, lectin, alternative, and extrinsic) and a terminal lytic pathway, it is an important part of both innate and adaptive immune responses ( 1– 3). The complement system is the most complex of the immunological and hematological pathways in human biology. Finally, we discuss the diagnostic potential of sMAC for diagnostic and prognostic applications and potential utility as a companion diagnostic.
Here, we review the structural differences between sMAC and its membrane counterpart, MAC, and examine sMAC immunobiology with respect to its presence in body fluids in health and disease. Despite decades of scientific interest in sMAC, the mechanisms regulating its formation in healthy individuals and its biological functions in both health and disease remain poorly understood. sMAC is present in blood and other body fluids under homeostatic conditions and there is abundant evidence documenting changes in sMAC levels during infection, autoimmune disease and trauma. To date no complement-mediated function has been identified for sMAC. sMAC is a unique complement activation macromolecule as it is comprised of several different subunits. sMAC is a member of the MACPF/cholesterol-dependent-cytolysin superfamily of pore-forming molecules that insert into lipid bilayers and disrupt cellular integrity and function. The soluble membrane attack complex (sMAC, a.k.a., sC5b-9 or TCC) is generated on activation of complement and contains the complement proteins C5b, C6, C7, C8, C9 together with the regulatory proteins clusterin and/or vitronectin.
1CNine Biosolutions, LLC, Birmingham, AL, United States.Barnum 1*, Doryen Bubeck 2 and Theresa N.
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