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At least 307 records · Page 17Linked to original sources
PubMed1989

Reconstitution of murine resident peritoneal macrophages for antibody-dependent cellular cytotoxicity by homologous serum Clq.

Mouse resident peritoneal macrophages (PM) were reconstituted in their response to activation for antibody-dependent cellular cytotoxicity (ADCC) for sheep erythrocyte targets (SRBC) by subhemolytic dilutions of homologous or autologous sera. ADCC-responsive inflammatory PM were largely unaffected in their activation by exogenous serum. Augmentation of resident PM for ADCC by homologous serum was correlated with the complement-activating potential of the mouse monoclonal anti-SRBC IgG isotype in that serum augmented IgG gamma 2a greater than IgG gamma 2b much greater than IgG gamma 1. The active component of mouse serum was heat-labile at 56 degrees C for 30 min and was present in both C5-deficient AKR and C5-sufficient homologous C3H mouse sera. Western blot analysis of the cell lysates for Clq confirmed that oil-elicited and thioglycollate-elicited inflammatory PM had greater levels of endogenous Clq than did resident PM which correlated with their innate responsiveness for ADCC activation. Depletion of Clq from serum by immunoprecipitation with IgG antibody to Clq or by ion exchange chromatography removed the active reconstituting activity for ADCC. Purified mouse Clq (0.4 microgram) partially replenished the ADCC augmenting activity of Clq-depleted AKR mouse serum. SRBC targets preopsonized with IgG gamma 2a and purified mouse Clq (0.075-5.0 microgram/ml) fully reconstituted the ADCC response of resident PM similar to homologous serum indicating that the major active component of serum was Clq. Thus resident PM with low endogenous levels of Clq were reconstituted for ADCC by the addition of exogenous Clq, whereas inflammatory PM with sufficiently high endogenous levels of Clq were not further enhanced by exogenous Clq. Our findings indicate that Clq may provide an essential second signal in concert with Fc receptor binding of IgG to initiate ADCC activation of macrophages.

Animals↗
PubMed1987

IgG binding to cytoskeletal intermediate filaments activates the complement cascade.

The cellular plasma membrane becomes permeable to macromolecules during the cell injury process. This results in exposure of the interior of the cell to plasma proteins and to high-affinity binding of the Fc part of IgG to intermediate filaments (Hansson, G K, Starkebaum, G A, Benditt, E P & Schwartz, S M, Proc natl acad sci USA 81 (1984) 3103). Such IgG binding could be an early step in a process that serves to eliminate the injured cell. We have now identified its effect on the complement system. Intermediate filaments were reconstituted in vitro from purified vimentin, and incubated with plasma proteins. Cross-linker experiments showed binding of the heavy chain of IgG to vimentin, indicating that the vimentin protein carries an Fc-binding site. In contrast, no direct binding of complement factor Clq to vimentin could be detected. Binding of both IgG and Clq could, however, be detected by immunofluorescence when cytoskeletons of cultured endothelial cells were incubated with fresh serum. Therefore, IgG binding to filaments in the presence of serum is accompanied by Clq binding to IgG. This was in turn followed by fixation of C4 and C3 to intermediate filaments in a process that was dependent on both Ca2+, Mg2+ and Clq, indicating that it was part of a complement activation via the classical pathway. Exposure of fresh serum to intermediate filaments also resulted in production of the anaphylatoxic complement cleavage fragment. C3a, with a dose-response relationship between the amount of filaments present and the amount of C3a generated. Chemotactic activity towards granulocytes and monocytes was also generated by exposure of serum to intermediate filaments, and this activity was dependent on the presence of complement factor C5 and on the classical complement activation cascade, implying that it was due to the C5a peptide. Exposure of the interior of the cell to plasma proteins thus results in binding of IgG to intermediate filaments and activation of the complement cascade via the classical pathway. This, in turn generates bioactive mediators which may recruit leukocytes to the injured cell (C5a) and have profound effects on vascular permeability (C3a, C5a). We propose that this is part of a scavenger mechanism for the elimination of damaged cells.

Binding Sites↗
PubMed1987

Identification of erythro-beta-hydroxyasparagine in the EGF-like domain of human C1r.

Previous studies [(1987) Biochem. J. 241, 711-720] have shown that position 150 of human C1r is occupied by a modified amino acid that, after acid hydrolysis, yields erythro-beta-hydroxyaspartic acid. In view of further investigations on the nature of this residue, peptide CN1a T8/T9 TL8 (positions 147-155) was isolated from C1r A chain by CNBr cleavage followed by enzymatic cleavages by trypsin and thermolysin. Amino acid analysis, sequential Edman degradation and FAB-MS of this peptide indicate that the residue at position 150 is an erythro-beta-hydroxyasparagine resulting from post-translational hydroxylation of asparagine.

Amino Acids↗
PubMed1988

Enzymatic alteration of C1q, the collagen-like subcomponent of the first component of complement, leads to cross-reactivity with type II collagen.

Native serum C1q, the collagenous-like subcomponent of the first component of complement, is not recognized by polyclonal anti-collagen type II antibodies. However, when purified C1q was subjected to limited proteolysis by collagenase it showed antigenic cross-reactivity with collagen type II. The same cross-reactivity was observed with hemolytically active C1q in synovial fluids of patients with rheumatoid arthritis (RA), whereas C1q from synovial fluids of patients with osteoarthritis (OA), villo-nodular synovitis and ankylosing spondylitis was not recognized by this antibody. However, incubation of synovial fluid C1q of OA patients with synovial fluid leucocytes from RA patients led to an alteration of OA-C1q which was now recognized by the anti-collagen type II antibody.

Animals↗