Lung injury complement activation

Till GO, Johnson KJ, Kunkel R, Ward PA (1982) Intravascular activation of complement and acute lung injury. Dependency on neutrophils and toxic oxygen metabolites. J Clin Invest 69 112611-35. 

The incidence of transfusion-related acute lung injury is 0.16-0.24% per transfusion of blood products and is the cause of 15% of all fatal complications of blood transfusion (11). Specific antigen-antibody reactions involving donor antibodies specific for leukocyte antigens of the recipients cause activation of neutrophils and aggregation in small pulmonary vessels (11). The complement and cytokine cascade is activated, leading to capillary leakage. 

A recent report by Parsons et a/." presented evidence for simultaneous elevation of complement fragments and measurable levels of endotoxin in plasma from patients with ARDS. Because complement activation by toxins and by other mechanisms" is thought to cause neutrophil and platelet activation" and subsequent generation of toxic oxygen species and eico-sanoids various strategies known to activate intravascular complement have been used to examine the role of eicosanoids in lung injury . To... 

Tvedten, H.W., Till, G.O. and Ward, P.A. (1985). Mediators of lung injury in mice following systemic activation of complement. Am. ]. Pathol, 119, 92-100... 

One question that has never been properly answered is What is the biological function of CVF in cobra venom Cobra venom factor in purified form can be considered nontoxic. When introduced into the bloodstream of an animal, complement activation with consumption of complement component occurs (41). Intravascular complement activation may have some side effects, such as sequestration of neutrophils to the lungs with subsequent injury to lung tissue (42). However, unless massive amounts of CVF are administered i.v., the consequences of intravascular complement activation by CVF are insignificant compared with the toxic effects of the other venom components, particularly the neurotoxins and membrane toxins. It appears, therefore, that local complement activation at the site of venom injection into the prey animal may be the beneficial effect of CVF for the cobra. Local complement activation by CVF will release the anaphylatoxins C3a and C5a which, in turn, will cause the degranulation of mast cells and basophils, with subsequent increase of the vascular permeability. The increased vascular permeability locally at the site of venom... 

G. 0. Till, K. J. Johnson, R. Kunkel, and P. A. Ward. Intravascular activation of complement and acute lung injury. 1982.7 Clin Invest. 69, 1126-1135. 

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