Lectin Complement Pathway and Its Bloody Interactions in Brain Ischemia
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Stroke is associated with vascular events that follow the initial insult and involve the activation of several blood-borne cascades including coagulation, contact/kinin, and complement cascade. There is growing evidence implicating the complement system as a co-ordinator of these cascades in brain ischemia.1–4 Although full complement cascade activation leads to cell lysis, complement components activated along the cascade (upstream of the final event) have active parts in inflammatory processes, implying they are in intimate cross talk with the other systems.
The complement system is a physiological component of innate immunity, which is activated on recognition of danger signals, the so-called damage-associated molecular patterns, in addition to pathogen-associated molecular patterns.5–7 Damage-associated molecular patterns include glycoproteins and proteins from the extracellular matrix, intracellular proteins, DNA or RNA fragments, and heat-shock proteins, all produced when tissue homeostasis is altered by pathological condition. Different signals lead to the activation of different complement activation pathways, namely, the classical (activated on binding antibodies, C-reactive protein, apoptotic cells, and nucleic acids), lectin (LP, activated on recognition of carbohydrate patterns), alternative (constitutively active and working as an amplifying loop of complement) and extrinsic (activated by tissue factor, and thrombin) pathways, all generating cleaved active fragments by cascade-like proteolytic reactions.6,8
The LP seems to have a vital role in brain ischemia.6 This pathway depends on initiator molecules including mannose-binding lectin (MBL), ficolin-1, -2, and -3, and collectin-11 that can recognize and bind carbohydrates exposed on the surface of altered or damaged cells, including endothelial cells.6 They normally circulate complexed with MBL-associated serine proteases (MASPs). On binding to their ligands, the complexes become activated, promoting downstream complement activation.9 LP active complexes can also cleave coagulation factors and may, thus, directly contribute to thrombosis.1,4,10