Antineutrophil cytoplasmic antibodies induce decreased CD62L expression and enhanced metabolic activity in monocytes.
Monocyte in vitro activation by antimyeloperoxidase (anti-MPO)- and antiproteinase-3 (anti-PR3)-positive sera, corresponding immunoglobulin G (IgG) fractions and monoclonal antibodies against MPO and PR3 was evaluated. The expression of adhesion molecules, l-selectin (CD62L) and CR3 (CD11b), involved in leucocyte endothelial adhesion, and metabolic activity, measured as the production of hydrogen peroxide, were analysed. Decreased expression of CD62L was demonstrated in monocytes after incubation with antineutrophil cytoplasmic antibody (ANCA)-positive sera. This finding was not accompanied by changes in CD11b expression. Metabolic activity was increased in monocytes after incubation with ANCA-positive IgG fractions as well as after incubation with monoclonal anti-MPO and anti-PR3. These findings support the concept that the pathophysiological effect of ANCA is partly mediated through the action on crucial events in monocyte activation, such as CD62L downregulation and oxygen radical production.
Wikman
A
A
Department of Medicine, Division of Clinical Immunology and Transfusion Medicine, Karolinska Hospital and Karolinska Institutet, Stockholm, Sweden. agneta.wikman@ks.se
Fagergren
A
A
Forslid
J
J
Jacobson
S H
SH
Johansson
S G O
SG
Lundahl
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001711:Biotransformation; D039481:CD11b Antigen / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D019041:L-Selectin / Q000097:blood* / Q000276:immunology; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D053146:Myeloblastin; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009195:Peroxidase / Q000276:immunology / Q000378:metabolism; D012697:Serine Endopeptidases / Q000276:immunology / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D019268:Antibodies, Antineutrophil Cytoplasmic; D000911:Antibodies, Monoclonal; D039481:CD11b Antigen; D007074:Immunoglobulin G; D019041:L-Selectin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D006861:Hydrogen Peroxide; D009195:Peroxidase; D012697:Serine Endopeptidases; D053146:Myeloblastin; D013755:Tetradecanoylphorbol Acetate