Reaction mechanism of the alternative pathway of complement fixation

PJ Lachmann, P Nicol - The Lancet, 1973 - Elsevier
PJ Lachmann, P Nicol
The Lancet, 1973Elsevier
The alternative pathway of complement activation is essentially a C3b-feedback pathway by
which the principal conversion product of C3 generates more C3-converting enzyme.
Activation of the alternative pathway by yeast or endotoxin or the appropriate
immunoglobulin (eg, IgA) aggregates is wholly dependent on the feedback mechanism and
it is not clear at what point they act. The activity of this feedback pathway is homœostatically
controlled by the activity of the C3b inactivator, and if this factor is absent or removed the …
Abstract
The alternative pathway of complement activation is essentially a C3b-feedback pathway by which the principal conversion product of C3 generates more C3-converting enzyme. Activation of the alternative pathway by yeast or endotoxin or the appropriate immunoglobulin (e.g., IgA) aggregates is wholly dependent on the feedback mechanism and it is not clear at what point they act. The activity of this feedback pathway is homœostatically controlled by the activity of the C3b inactivator, and if this factor is absent or removed the alternative pathway is activated to the state of exhaustion. The complement- inactivating factor in cobra venom is able to generate a C3–convertase in the absence of C3b, and to this extent is an analogue of C3b. The C.V.F. complex seems to generate C3–convertase from G.B.G. by an enzymatic reaction which releases no products. This would explain many of the properties of the C.V.F. C3–convertase.
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