Complement and the central nervous system: emerging roles in development, protection and regeneration

Abstract

As expanding research reveals the novel ability of complement proteins to promote proliferation and regeneration of tissues throughout the body, the concept of the complement cascade as an innate immune effector has changed rapidly. In particular, its interactions with the central nervous system have provided a wealth of information regarding the ability of complement proteins to mediate neurogenesis, synaptogenesis, cell migration, neuroprotection, proliferation and regeneration. At numerous phases of the neuronal and glial cell cycle, complement proteins exert direct or indirect influence over their behavior and fate. Neuronal stem cells differentiate and migrate in response to complement, and it prevents injury and death in adult cells in response to toxic agents. Furthermore, complement proteins promote survival via anti-apoptotic actions, and can facilitate clearance and regeneration of injured tissues in various models of CNS disease. In summary, we highlight the protean abilities of complement proteins in the central nervous system, underscoring an exciting avenue of research that has yielded greater understanding of complement's role in central nervous system health and disease.

Mannose-Binding Lectin Promotes Local Microvascular Thrombosis After Transient Brain Ischemia in Mice

“…41 Furthermore, complement proteins can facilitate regeneration in various models of central nervous system disease. 42 Therefore, the possibility that MBL may play different roles during the recovery phase cannot be excluded.…”

Cancer and the Complement Cascade

“…The proliferative abilities of the anaphylatoxins C3a and C5a have been documented repeatedly (22)(23)(24) and reveal the participation of several signal transduction pathways with known links to neoplastic progression (Table 1). C3a receptor (C3aR) and C5a receptor (C5aR) are both coupled to G-proteins (25,26).…”

“…Thus, it is not surprising that evidence for complement-mediated disease pathogenesis has centered primarily on dysfunctional immunity caused by the absence, alteration, or overactivity of complement proteins (19)(20)(21). The relationship grows even more complex with the growing body of evidence suggesting that complement proteins mediate cellular turnover, growth, and regeneration, including bone marrow stem cell engraftment, bone and cartilage development, neurogenesis, synaptogenesis, white matter healing, and regeneration of the liver, limb, and lens (22)(23)(24).…”

Soluble membrane attack complex is diagnostic for intraventricular shunt infection in children

“…Children treated with antibiotics prior to shunt tap (because of the possible effect antibiotics could have on complement activation), shunt infection within the previous 180 days (to insure that we had a cohort clear of residual infection and that residual sMAC levels would have returned to baseline), and children with newly diagnosed tumors were excluded from this analysis ( Table 1). Patients with newly diagnosed tumors were excluded from analysis due to potential confounding effects of malignant tumors on complement activation (36,37). Patient demographics are shown in Table 2.…”