Antibody-independent classical complement pathway activation and homologous C3 deposition in xeroderma pigmentosum cell lines.
Of human malignantly transformed cell lines, xeroderma pigmentosum (XP) cell lines were found to be highly susceptible to homologous complement (C): cells were opsonized by C3 fragments on incubation with diluted normal human serum. C3 fragment deposition on XP cells was Ca2+-dependent and occurred on live cells but not UV-irradiated apoptotic cells. (Ca2+ is required for activation of the classical C pathway via C1q and the lactin pathway via mannose binding lectin (MBL), and the surface of apoptotic cells usually activates the alternative C pathway.) In this study we tested which of the pathways participates in XP cell C3 deposition. In seven cell lines that allowed C3 deposition (i), Clq was shown to be essential but MBL played no role in C activation, (ii) Cls but not MASP bound XP cells for activation, (iii) no antibodies recognizing XP cells were required for homologous C3 deposition, and (iv) the alternative pathway barely participated in C3 deposition. Furthermore, the levels of C-regulatory proteins for host cell protection against C, decay-accelerating factor (DAF, CD55) and membrane cofactor protein (MCP, CD46), were found to be relatively low in almost all XP cell lines compared with normal cells. These results indicate that XP cells activate the classical C pathway in an antibody-independent manner through the expression of a molecule which directly attracts C1q in a C-activating form, and that relatively low levels of DAF and MCP on XP cells facilitate effective C3 deposition. The possible relationship between the pathogenesis of XP and our findings is discussed.
Kurita
M
M
Department of Immunology, Osaka Medical Centre for Cancer and Cardiovascular Diseases, Higashinari-ku, Osaka 537, Japan.
Matsumoto
M
M
Tsuji
S
S
Kawakami
M
M
Suzuki
Y
Y
Hayashi
H
H
Toyoshima
K
K
Seya
T
T
D000906:Antibodies / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002461:Cell Line, Transformed; D037222:Collectins; D015922:Complement C1q / Q000378:metabolism; D003173:Complement C1s / Q000378:metabolism; D003176:Complement C3 / Q000378:metabolism*; D003171:Complement Pathway, Classical; D006801:Humans; D037102:Lectins / Q000378:metabolism; D008351:Mannans / Q000378:metabolism; D014983:Xeroderma Pigmentosum / Q000276:immunology* / Q000378:metabolism
D000906:Antibodies; D002352:Carrier Proteins; D037222:Collectins; D003176:Complement C3; D037102:Lectins; D008351:Mannans; D015922:Complement C1q; D003173:Complement C1s