Activation of Complement Component C5
Abstract
Activation of Complement Component C5 COMPARISON OF C5 CONVERTASES OF THE LECTIN PATHWAY AND THE CLASSICAL PATHWAY OF COMPLEMENT* Received for publication,September 11, 2007, and in revised form, December 5, 2007 Published, JBC Papers in Press,January 18, 2008, DOI 10.1074/jbc.M707591200 Nenoo Rawal1, Rema Rajagopalan, and Veena P. Salvi From the Department of Biochemistry, University of Texas Health Science Center, Tyler, Texas 75708 Although the initiating complex of lectin pathway (called M1 in this study) generates C3/C5 convertases similar to those assembled by the initiating complex (C1) of the classical path- way, activation of complement component C5 via the lectin pathway has not been examined. In the present study kinetic analysis of lectin pathway C3/C5 convertases assembled on two surfaces (zymosan and sheep erythrocytes coated with mannan (EMan)) revealed that the convertases (ZymM1,C4b,C2a and EManM1,C4b,C2a) exhibited a similar but weak affinity for the substrate, C5 indicated by a high Km (2.73–6.88 M). Very high affinity C5 convertases were generated when the low affinity C3/C5 convertases were allowed to deposit C3b by cleaving native C3. These C3b-containing convertases exhibited Km (0.0086–0.0075 M) well below the normal concentration of C5 in blood (0.37 M). Although kinetic parameters, Km and kcat, of the lectin pathway C3/C5 convertases were similar to those reported for classical pathway C3/C5 convertases, stud- ies on the ability of C4b to bind C2 indicated that every C4b deposited on zymosan or EMan was capable of forming a con- vertase. These findings differ from those reported for the classical pathway C3/C5 convertase, where only one of four C4b molecules deposited formed a convertase. The potential for four times more amplification via the lectin pathway than the classical pathway in the generation of C3/C5 convertases and production of pro-inflammatory products, such as C3a, C4a, and C5a, implies that activation of complement via th
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Cited By (1)
References (5)
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