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*Immune System and Disorders
The Journal of Immunology, 2006, 176: 1305-1310.
Copyright © 2006 by The American Association of Immunologists

BRIEF REVIEWS

The Central Role of the Alternative Complement Pathway in Human Disease1

Joshua M. Thurman* and V. Michael Holers2,{dagger}

* Division of Nephrology and Hypertension and {dagger} Division of Rheumatology, Departments of Medicine and Immunology, University of Colorado Health Sciences Center, Denver, CO 80262

The complement system is increasingly recognized as important in the pathogenesis of tissue injury in vivo following immune, ischemic, or infectious insults. Within the complement system, three pathways are capable of initiating the processes that result in C3 activation: classical, alternative, and lectin. Although the roles that proinflammatory peptides and complexes generated during complement activation play in mediating disease processes have been studied extensively, the relative contributions of the three activating pathways is less well understood. Herein we examine recent evidence that the alternative complement pathway plays a key and, in most instances, obligate role in generating proinflammatory complement activation products in vivo. In addition, we discuss new concepts regarding the mechanisms by which the alternative pathway is activated in vivo, as recent clinical findings and experimental results have provided evidence that continuous active control of this pathway is necessary to prevent unintended targeting and injury to self tissues.




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