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PubMedDate not supplied

In vivo activation of serum complement by contrast media: a clinical study.

The study was designed to confirm complement system activation in vivo in man after intravenous injection of contrast media for brain CT scan enhancement. Four currently available components were tested: C1q, C3 activator, C3c, and C4 after intravenous injection of seven different contrast media: diatrizoate, metrizoate, iothalamate, ioxithalamate, ioxaglate, metrizamide, iopamidol. The complement system was indeed activated by certain control media, but no correlation with clinical reactions or with hypertonicity, ionic or nonionic formulation, or protein binding could be found. However, a correlation was found to some extent between the lipid solubility and the activity on the complement system. Addition of calcium salts definitely inhibited the complement system activation induced by metrizoate and ioxaglate.

Brain↗
PubMed1979

Complement.

Explore the source record for details and available documents.

Bacterial Infections↗
PubMed1985

Complement activation associated with active cytomegalovirus infection in renal transplant patients, and its absence in transplant rejection episodes.

In 20 patients with a cadaveric renal allograft, serial measurements were made of the serum complement factors C3, C4, factor B (FB), and C3d, the stable conversion product of C3. Measurements were started immediately before transplantation and continued thereafter once a week to investigate whether these assays help to differentiate between acute allograft rejection (R) and an active cytomegalovirus (CMV) infection. Fifteen patients had one or more R episodes, and 9 patients suffered from an active CMV infection. Six patients had an R episode and subsequently a CMV infection 13-64 days after R. No significant changes were found in the levels of C3, C4, and FB during R or CMV infection. C3d levels remained unchanged or decreased slightly during R. However, there was a 43-500% increase in the C3d level during CMV infection. This difference in the behavior of levels of C3d during R and CMV infection is significant (P less than 0.01), and suggests that serial measurements of C3d may be useful in differentiating CMV infection from R after renal transplantation.

Adult↗
PubMed1997

Immunopathological observations after xenogeneic liver perfusions using donor pigs transgenic for human decay-accelerating factor.

BACKGROUND: Donor pigs transgenic for human decay-accelerating factor (hDAF) were used in a xenogeneic ex vivo liver perfusion model to study the effect of this modification on the development of hyperacute rejection. METHODS: Three transgenic pigs were hepatectomized after hypothermic portal and transaortal gravity perfusion. Livers from six nontransgenic pigs served as controls. All livers were perfused for 3 hr with human blood from two donors diluted to a hematocrit of 30%. Particular importance was placed on the use of an optimal perfusion technique incorporating the floating suspension of the organs in a waterbath and intermittent external pressurization. Biochemical, physiological, and immunological parameters were assessed. Tissue specimens taken before and after perfusion were analyzed using routine histology, electron microscopy, and immunohistology. RESULTS: Complement activation was more pronounced in the control group. AP50 and CH50 values fell to about 60% of the initial levels in control experiments, whereas they remained at 80% of the initial levels during perfusion of hDAF livers. After 180 min, pig tumor necrosis factor alpha levels were 7862+/-1645 pg/ml for unmodified livers and 2830+/-734 pg/ml in the hDAF group. Human tumor necrosis factor alpha levels were similar in both groups. Control livers showed marked morphological alterations and distinct deposition of complement factors, whereas livers expressing hDAF showed no signs of hepatocellular necrosis and almost no complement deposition beyond C3 activation. CONCLUSIONS: These results confirm that the transgenic expression of the human complement regulatory protein hDAF reduces complement activation and prevents hyperacute rejection in a xenogeneic liver perfusion model over the 3-hr evaluation period used in this study.

Animals↗
PubMedDate not supplied

Change of complement system predicts the outcome of patients with severe thermal injury.

To establish the clinical relevance of the changes in the complement system in patients with thermal injury, we studied 20 patients who had third-degree burns on more than 60% of total body surface area. Their levels of the C3, C4, soluble C5b-9, and functional hemolytic activities of total (CH50) and alternative (AH50) complement pathways were sequentially measured for 2 weeks after thermal injury. All patients showed low C3 levels initially but increased C3 levels in the following days. The increasing trend of C3 levels was prominent in survivors but transient and diminished in nonsurvivors. The change of levels of C3, CH50, and AH50 was closely associated with one another, and their chronological trends related to the survival of patients (P =.0060,.0064 and.0066, respectively). The recovery of C3, AH50, and CH50 to normal or supranormal level during the early treatment period relates to the survival of patients with thermal injury. The failure of recovery of the complement system indicates a poor prognosis for patients and the monitoring of complement system might be beneficial in the care of patients with thermal injury.

Adult↗
PubMed1984

The role of different K antigens of Escherichia coli in phagocytosis by polymorphonuclear leukocytes.

The importance of K antigens from six strains of Escherichia coli for the interaction with polymorphonuclear leukocytes (PMNL) was studied. The major factor influencing this interaction was the ability of strains to activate complement by the classical route during opsonisation, this process being reduced for most K-positive strains. Interference of K antigens with the functioning of common pili as adhesions of eukaryotic cells was not observed nor a toxic effect of K antigens on PMNL.

Antibodies, Bacterial↗
PubMed1985

Complement effector mechanisms in health and disease.

Complement is an effector system able to mediate a number of biological activities in vitro and in vivo. Most familiar is the ability of the system to mediate the lytic destruction of numerous kinds of cells and pathogenic organisms including bacteria, viruses, and virus-infected cells. In addition, the complement system also activates neutrophils, monocytes, basophils, mast cells, and lymphocytes to perform specialized functions. While generally considered to be confined to the effector side of immune reactions, recent evidence indicates that the complement system also directly recognizes and is triggered by a number of bacteria and viruses as well as virus-infected cells in the absence of antibody. In such reactions, complement fulfills the recognition role normally associated with the antibody molecule or immune lymphocyte. The complement system may thus also function as a natural surveillance system operative prior to the induction of specific immunity. Involvement of the complement system in biological reactions has been ascertained by several techniques over the years. These include quantitation of individual complement components in human sera and demonstration of complement deposition in diseased tissues in human diseases and in experimental diseases in animals. Such techniques, however, have limitations in specificity and sensitivity. Assays which detect specific features of the complement activation process have become available in recent years. These tests detect the physical, chemical, or antigenic changes characteristic of the complement activation process. These assays are extremely specific and quantitative; furthermore, most are usable with samples from patients. Three general approaches have been utilized to develop such specific quantitative assays for complement activation. The first includes assays which quantitate activation-specific limited proteolysis of the complement components. The second type of assay includes tests which detect and quantitate new antigens or other activation-specific antigenic changes. The third category is represented by assays which detect and quantitate the protein-protein complexes characteristic of the activation process. Examples of tests presenting each of these approaches are given.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2004

Immune complex-stimulated production of interleukin-12 in peripheral blood mononuclear cells is regulated by the complement system.

Immune complexes (IC) can induce cytokine production in vitro. While immune aggregates (IA) consisting of heat-aggregated gamma globulin (HAGG) as model IC increased interleukin (IL)-10 levels in cell cultures with native human serum, IL-12p40/p70 production was inhibited. Three series of experiments suggested that the effects of IA on IL-12 production depended on a functionally intact complement system: (1) heat-inactivation of serum inverted the inhibitory effect of IA on IL-12p40/p70 production; (2) IA-induced IL-12p40 production in a C4 deficient serum was lowered by addition of C4; and (3) addition of the peptide compstatin, which blocks C3 activation, mimicked the effects of heat inactivation on IL-12p40 levels. Neutralization of IL-12 resulted in modestly increased IL-10 levels, while neutralization of IL-10 had no effects on IL-12p40 production. IA-induced production of IL-10 was partially blocked by anti-Fcgamma RII antibodies, whereas Fcgamma R or CR blockade had no effect on IL-12p40 production. IC and local or systemic complement activation characterize rheumatoid arthritis, systemic lupus erythematosus and many malignancies. Different and complement-dependent effects on the production of IL-10 and IL-12 can be of importance in these diseases, where control of the complement system might be a way to direct IC-induced cytokine production in either a type 1 or type 2 direction.

Antigen-Antibody Complex↗
PubMed1984

The chemotactic activity of normal and complement-activated serum as measured by the leading-front method using a Boyden chamber.

The chemotactic activity in serum, defined as the attractant effect of serum on the migration of neutrophil granulocytes (PMN) has been investigated for the purpose of characterizing the major chemotactic factors in serum as measured by the leading-front technique, using a modified Boyden chamber. The chemotactic activity was measured in fresh and heated normal and activated serum and in serum fractions thereof separated by gel filtration. By gel filtration on Sephacryl S-200 a partly heat-labile C3-C5-associated chemotactic factor with molecular weight between 70,000 and 150,000 was isolated from fresh normal serum. The heat-labile chemotactic activity was destroyed by pronounced complement activation. Gel filtration of complement-activated serum on a Sephacryl S-200 column showed the existence of one C5-associated chemotactic factor with approximately 70,000 molecular weight and one unidentified factor with approximately 150,000 molecular weight, whereas no low molecular weight chemotactic activity was demonstrated. On the other hand, gel filtration of activated serum on a Sephadex G-75 column demonstrated one C5-associated chemotactic factor of approximately 70,000 molecular weight and one 10,000-50,000 molecular weight factor active only in the presence of 2% normal serum. This investigation suggests that the chemotactic activity in fresh normal serum is mediated by a partly heat-labile C3-C5-associated complex. In activated serum three chemotactic factors were demonstrated, one unidentified factor with 150,000 mol wt and two C5-dependent factors with 70,000 and 10,000-50,000 mol wt, the latter probably corresponding to C5a desarg. Accordingly, this study also suggests that C5a is not the only chemotactic factor generated in serum.

Blood Physiological Phenomena↗