Anti-mouse properdin TSR 5/6 monoclonal antibodies block complement alternative pathway-dependent pathogenesis.
The complement alternative pathway (AP) is a major contributor to a broad and growing spectrum of diseases that includes age-related macular degeneration, atypical hemolytic uremic syndrome, and preeclampsia. As a result, there is much interest in the therapeutic disruption of AP activity. Properdin, the only positive regulator of the AP, is a particularly promising AP target. Several issues need to be clarified before the potential for properdin-directed therapy can be realized. In this report we use a portion of the mouse properdin protein, expressed in a bacterial system, to raise rabbit polyclonal and hamster monoclonal antibodies that block properdin-dependent pathogenesis. These antibodies, when employed with AP-dependent mouse disease models, can help evaluate the feasibility of properdin-directed therapy.
Division of Rheumatology, Department of Internal Medicine, Washington University School of Medicine , St. Louis, Missouri.
Paula
P
Bertram
Antonina M
AM
Akk
Hui-fang
HF
Zhou
Lynne M
LM
Mitchell
Christine T N
CT
Pham
Dennis E
DE
Hourcade
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000494:pharmacology*; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D003170:Complement Pathway, Alternative / Q000187:drug effects*; D006224:Cricetinae; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D007166:Immunosuppressive Agents / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010196:Pancreatic Elastase; D011414:Properdin / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D011817:Rabbits; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D011994:Recombinant Proteins; D011414:Properdin; D010196:Pancreatic Elastase