Search PubMed⌕ Search
Home/Archive/PubMed

PubMed · 2249355

The complement system. Activation, modulation, and clinical relevance.

H W Lim
View original source ↗Export metadata ↓

Abstract

Activation of the classic or the alternative pathway of the complement system results in the generation of biologically active products and the assembly of MAC. Homeostasis is achieved by the presence of control proteins that modulate the activation at various levels. Complement proteins play an important role in the pathogenesis of several dermatologic disorders. Their deficiency is associated with impairment of host-defense; uncontrolled activation of the system results in the development of angioedema or chronic hemolysis.

Explore related subjects

Complement ActivationComplement Membrane Attack ComplexComplement Pathway, AlternativeComplement Pathway, ClassicalComplement System ProteinsHumansSkin DiseasesJournal ArticleReview

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

H W Lim. 1990. The complement system. Activation, modulation, and clinical relevance.. https://pubmed.ncbi.nlm.nih.gov/2249355/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2004

Causative factors behind poloxamer 188 (Pluronic F68, Flocor)-induced complement activation in human sera. A protective role against poloxamer-mediated complement activation by elevated serum lipoprotein levels.

Poloxamer 188 is a complex polydisperse mixture of non-ionic macromolecules. Adverse non-IgE-mediated hypersensitivity reactions occur in some individuals following intravenous injection of poloxamer 188-based pharmaceuticals, presumably via complement activation. Here we have delineated potential causal chemical and biological interactive factors behind poloxamer 188-induced complement activation in human serum specimens. We identified the molecular constituents inherent in poloxamer 188 preparations and studied their effect on generation of the two complement split products, SC5b-9 and Bb. Poloxamer 188 activated complement at sub-micellar concentrations and the results indicated the potential involvement of all three known complement activation pathways. The poloxamer-induced rise of SC5b-9 in human sera was abolished in the presence of a recombinant truncated soluble form of complement receptor type 1, thus confirming the role of C3/C5 convertases in the activation process. Poloxamer 188-mediated complement activation is an intrinsic property of these macromolecules and was independent of the degree of sample polydispersity, as opposed to other non-polymeric constituents. Poloxamer 188 preparations also contained unsaturated chains of diblock copolymers capable of generating SC5b-9 in human sera; this effect was terminated following the removal of double bonds by catalytic hydrogenation. By quasi-elastic light scattering, we established interaction between poloxamer and lipoproteins; interestingly, poloxamer-induced rise in SC5b-9 was significantly suppressed when serum HDL and LDL cholesterol levels were increased above normal to mimic two relevant clinical situations. This observation was consistent with previously reported data from patients with abnormal or elevated lipid profiles where no or poor complement activation by poloxamer 188 occurred. Our findings could provide the basis of novel approaches to the prevention of poloxamer-mediated complement activation.

Complement Activation↗
PubMed2004

Flow cytometric detection of complement-activating HLA antibodies.

BACKGROUND: Antibodies to HLA are implicated in allograft rejection; as a consequence, tests to identify them are indicated in organ transplantation. Flow cytometry (FC) may improve the outcome of organ transplantation. Although increasingly used, most of the available FC techniques do not discriminate between complement and noncomplement-activating antibodies. However, the clinical relevance of noncomplement-activating antibodies is controversial. Therefore, many laboratories still use the conventional complement-dependent microlymphocytotoxicity crossmatch (CDC-XM) alone or in combination with FC. METHODS: We describe a novel flow cytometric complement-dependent cytotoxicity crossmatch assay (FC-CDC-XM) that clearly identifies complement-binding HLA antibodies. With the aid of a three-color FACScan flow cytometer with a standard argon ion laser, we used fluorescence-conjugated anti-CD3 for the identification of T lymphocytes, anti-CD19 antibodies for the identification of B lymphocytes, and propidium iodide (PI) for the identification of damaged cells. Fluorescence-conjugated anti-CD3 and anti-CD19 antibodies were detected in the green (FL1) and orange (FL2) ranges of the spectrum. PI fluorescence was measured with the red (FL3) fluorescence channel. Gating of lymphocytes was performed using side scatter versus FL1 or FL2 dot plots for the identification of T and B lymphocytes, respectively. RESULTS: FC-CDC-XM was able to correctly identify all antibodies tested as specific to HLA class I (n = 18) or II (n = 4). CONCLUSIONS: The new FC-CDC-XM is more sensitive and more objective than the standard CDC-XM and can be used for pre- and posttransplant diagnoses and for the detection of other antibody-mediated cytotoxic reactions.

Complement Activation↗
PubMed2004

Assessment of complement activation during membrane-based plasmapheresis procedures.

Previous studies have suggested that plasmapheresis procedures using a separation membrane may activate the complement system and release anaphylatoxins. This study determines the content in C3a/C3a(des Arg) and C5a/C5a(des Arg) in plasma donations obtained by the new Haemonetics Filter Core (FC) procedure and compares it to Baxter Autopheresis C (Auto-C). FC performs sequential blood centrifugation and plasma filtration on a microporous polyethersulfone membrane, while Auto-C removes blood cells by simultaneous gravitation and filtration on a rotating nylon membrane. One group of 34 donors donated on FC and two groups of 30 and 10 donors on Auto-C. Plasma aliquots were taken from the plasma units within 30 min of the end of the collection procedures, frozen at < -30 degrees C and assessed for C3a and C5a at various time points of storage. Mean C3a/C3a(des Arg) in FC plasma (N = 34) was 1,151 (range: 526-2,991), 1,092 (range: 349-3498), and 507 (range: 307-815) ng/ml at time of collection and after 6 and 12 months of storage, respectively. Respective C5a/C5a(des Arg) was 26.6 (range 4.9-74), 18.9 (9.5-42.6), and 30.9 (range: 10.7-62.3) ng/ml. Mean C3a/C3a(des Arg) was higher in Auto-C (P < 0.001): 4,724 ng/ml (N = 10; range: 2,400-7 ,360) and > 4,149 ng/ml (N = 30; 2,408- > 6,430) after 3 and 18 months storage, respectively. Mean C5a/C5a(des Arg) was 32.1 ng/ml (N = 30; range: 10.6-57.2) after 18 months of storage. Complement activation in FC plasmas appears limited compared to Auto-C, suggesting better biocompatibility of this collection device and/or a favourable impact of the sequential cell centrifugation/filtration technology used. Further studies are needed to explain differences in complement activation between apheresis procedures and to assess clinical impacts, if any.

Complement Activation↗