Document Detail


Generation of C5-dependent bioactivity by tissue-bound anti-BMZ autoantibodies.
MedLine Citation:
PMID:  2754274     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We previously reported that complement-binding antibasement membrane zone (BMZ) autoantibodies can mediate complement-dependent directed migration and adherence of leukocytes to the BMZ in cryostat skin sections and that there is heterogeneity in the ability of anti-BMZ autoantibodies to mediate that response. Those observations suggested that directed migration and adherence of leukocytes to the BMZ might be dependent on the amount of complement-activating autoantibody deposited at the BMZ and the extent to which those antibodies could activate complement and generate C5-derived peptides (C5a, C5a des arg). In this study, we have examined the role of autoantibody concentration and C5 in mediating the adherence response. When cryostat skin sections were pretreated with anti-BMZ autoantibodies and subsequently incubated with neutrophils suspended in fresh serum, neutrophils adhered to the BMZ. Adherence was anti-BMZ autoantibody specific and proportional to anti-BMZ autoantibody concentration. To determine the role of C5 in mediating adherence, neutrophils were suspended in increasing concentrations of: 1) fresh serum, 2) heat-inactivated serum, 3) serum pretreated with antihuman C5, 4) serum pretreated with antihuman IgG, 5) C5-depleted serum, 6) purified C5, and 7) C5-depleted serum reconstituted with increasing concentrations of purified C5. The suspensions were then incubated with autoantibody-treated skin sections. The results showed a dose-dependent requirement for fresh serum and for C5-depleted serum reconstituted with increasing doses of C5. Adherence could be detected with C5 concentrations less than 200 ng/ml, which correspond to a C5a/C5a des arg concentration of 10(-8)-10(-9) molar. These results suggest that complement-dependent neutrophil adherence is a highly sensitive method for detecting and quantitating the ability of tissue-deposited anti-BMZ autoantibodies to activate complement and generate C5-derived bioactive peptides, for estimating the amount of C-activating anti-BMZ autoantibody deposited at the BMZ in vivo, and for evaluating the potential role of C-activating anti-BMZ autoantibodies in the pathogenesis of lesions.
Authors:
W R Gammon; K B Yancey; K L Mangum; J D Hendrix; C H Hammer
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of investigative dermatology     Volume:  93     ISSN:  0022-202X     ISO Abbreviation:  J. Invest. Dermatol.     Publication Date:  1989 Aug 
Date Detail:
Created Date:  1989-09-01     Completed Date:  1989-09-01     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0426720     Medline TA:  J Invest Dermatol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  195-200     Citation Subset:  IM    
Affiliation:
Department of Dermatology, University of North Carolina School of Medicine, Chapel Hill 27514.
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MeSH Terms
Descriptor/Qualifier:
Antibody Specificity
Autoantibodies / immunology*
Basement Membrane / immunology*,  physiology
Blood Physiological Phenomena
Cell Adhesion
Complement C5 / immunology*,  pharmacology
Humans
Neutrophils / physiology
Osmolar Concentration
Reference Values
Skin / immunology*
Grant Support
ID/Acronym/Agency:
AR30475/AR/NIAMS NIH HHS; AR37446/AR/NIAMS NIH HHS; RR00046/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Autoantibodies; 0/Complement C5

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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