Studies on the mechanisms of allergen-induced activation of the classical and lectin pathways of complement.
Allergen extracts are efficient activators of the complement system trough the classical pathway. Involvement of the lectin pathway was not previously studied. To further examine the mechanism of complement activation by allergens, in vitro experiments, which covered early steps both of classical and lectin pathways, were performed. Two types of allergens used in these studies: parietaria (PA) and house dust (HD) mite extracts. These allergen extracts bound to the globular head of C1q and interacted with purified mannan-binding lectin (MBL) as measured by solid-phase ELISA. None of the allergen extracts was able to activate human C1 in vitro, as measured by the determination of the split products of C1s in a reconstituted precursor C1 preparation. Neither the HD nor the PA extracts induced C4d generation above background in the serum of three subjects with hypogammaglobulinaemia but normal complement haemolytic activity. After reconstitution to normal level with purified human IgG, allergen extracts induced C4d formation above control at a level comparable to that measured in normal serum incubated with the same amounts of the extracts. HD-induced C4d generation was about the same comparable in MBL-depleted serum and in normal sera. In contrast PA induced no C4d formation in the MBL-depleted serum, whereas reconstitution with purified MBL restored C4d generation. These in vitro findings indicate that although the allergen extracts can bind purified C1q and MBL, they require IgG for efficient complement activation. Depending on the allergens, this activation may be initiated through C1, MBL, or both.
Varga
Lilian
L
3rd Department of Medicine, Faculty of Medicine, Semmelweis University, H-1125 Budapest, Kútvölgyi str 4, Hungary.
Szilágyi
Katalin
K
Lõrincz
Zsolt
Z
Berrens
Lubertus
L
Thiel
Steffen
S
Závodszky
Peter
P
Daha
Mohamed R
MR
Thielens
Nicole M
NM
Arlaud
Gerard J
GJ
Nagy
Kálmán
K
Späth
Peter
P
Füst
George
G
D000361:Agammaglobulinemia / Q000097:blood / Q000276:immunology; D000485:Allergens / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D015922:Complement C1q / Q000378:metabolism; D003173:Complement C1s / Q000032:analysis; D003181:Complement C4 / Q000096:biosynthesis; D015935:Complement C4b; D003170:Complement Pathway, Alternative / Q000276:immunology*; D003171:Complement Pathway, Classical / Q000276:immunology*; D004391:Dust; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D037601:Mannose-Binding Lectin / Q000378:metabolism; D008925:Mites / Q000276:immunology; D032403:Parietaria / Q000276:immunology; D010446:Peptide Fragments / Q000096:biosynthesis; D011058:Pollen / Q000276:immunology; D025941:Protein Interaction Mapping
D000485:Allergens; D003181:Complement C4; D004391:Dust; D007074:Immunoglobulin G; D037601:Mannose-Binding Lectin; D010446:Peptide Fragments; D015922:Complement C1q; D015935:Complement C4b; C032261:complement C4d; D003173:Complement C1s