Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Complement C3a”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,027 records · Page 57Linked to original sources
PubMed1988

Anaphylatoxin levels in human vitreous humor.

The complement system is involved not only in host defense against infection but also in autoimmune tissue damage. Using a radioimmunoassay, we sought to measure levels of C3a, C4a and C5a (activated complement fragments with anaphylatoxin functions) in human vitreous humor from eyes with and without vitreal inflammation. Vitreous from 11 patients with clinical evidence of vitritis (Group 2) had significantly higher levels of protein, C3a and C4a and significantly higher ratios of these anaphylatoxins to protein than vitreous from 19 patients without clinical evidence of vitritis (Group 1). The finding that not only the absolute levels of anaphylatoxins but also the ratios of anaphylatoxins to protein were significantly higher in vitreous from Group 2 than vitreous from Group 1 or normal plasma suggested that complement activation was taking place in inflamed vitreous. Because of irreversible binding to leukocytes, C5a is difficult to measure and correlate with complement activation, and we were unable to detect it in any vitreous sample.

Anaphylatoxins↗
PubMed1998

Complement activation by diesel exhaust particles (DEP).

The effect of diesel exhaust particles (DEP) on the hemolytic activity of human serum complement was investigated. Previous treatment of human serum with DEP extracts at 37 degrees C decreased the hemolytic activity of human serum complement dose dependently, to 20% of its original value. This decrease in complement activity by DEP extracts was observed with previous incubation at 37 degrees C but not at 4 degrees C. A decrease in complement activity was observed after previous incubation at 37 degrees C in the presence of EGTA/Mg but not in the presence of EDTA, indicating that the alternative pathway of the complement system had been activated by DEP extracts. Activation of the complement system by DEP extracts was further demonstrated by observation of the cleavage of the third component of the complement (C3) in serum to C3b with immunoelectrophoresis using goat anti-human C3 antiserum. This cleavage of C3 was similarly observed in the presence of EGTA/Mg, indicating the activation of the alternative pathway of the complement system by DEP extracts. These results indicate that DEP can activate the alternative pathway of the complement system, resulting in a decrease in the hemolytic activity of complement and in the production of biologically active degradation products of complement proteins such as C3a. The biological significance of the activation of the complement by DEP in the alveolus is discussed in relation to the influx of neutrophiles.

Animals↗
PubMed1990

Inflammatory mediators in the vitreous humor of AIDS patients with retinitis.

We measured levels of protein, of complement-derived anaphylatoxins (C3a, C4a, and C5a), and of the lymphokines interleukin-2 and gamma interferon, in vitreous humor from 10 AIDS patients with vitritis and retinitis (group 1). We compared these measurements with levels in vitreous from 7 patients with vitritis but without AIDS (group 2), 10 patients with vitreous hemorrhages (group 3), and 20 patients with retinal detachments or epiretinal membranes without clinical evidence of vitreal inflammation (group 4). Vitreous humor from 10 AIDS patients had measurable levels of interleukin-2 in three of nine samples, gamma interferon in six of nine samples, C3a and C4a in all ten samples, and C5a in only one of ten samples. Vitreous humor from group 1 did not differ significantly from vitreous from group 2. On the other hand, vitreous from group 1 had significantly higher levels of gamma interferon, C3a, and C4a, and higher ratios of these anaphylatoxins to protein, in comparison to vitreous in groups 3 and 4. The results of this study suggest that vitreous humor from AIDS patients with retinitis contains activated complement and may contain interleukin-2 and gamma interferon. Viral retinitis is associated with the presence of lymphokines in vitreous humor. Additionally, anaphylatoxin and gamma interferon levels, but not interleukin-2 levels, correlate with vitreal inflammation. This is the first study to measure interleukin-2, gamma interferon, and C5a levels in human vitreous humor.

Acquired Immunodeficiency Syndrome↗
PubMed2006

First identification of a chemotactic receptor in an invertebrate species: structural and functional characterization of Ciona intestinalis C3a receptor.

In mammals, the bioactive fragment C3a, released from C3 during complement activation, is a potent mediator of inflammatory reactions and exerts its functional activity through the specific binding to cell surface G protein-coupled seven-transmembrane receptors. Recently, we demonstrated a Ciona intestinalis C3a (CiC3a)-mediated chemotaxis of hemocytes in the deuterostome invertebrate Ciona intestinalis and suggested an important role for this molecule in inflammatory processes. In the present work, we have cloned and characterized the receptor molecule involved in the CiC3a-mediated chemotaxis and studied its expression profile. The sequence, encoding a 95,394 Da seven-transmembrane domain protein, shows the highest sequence homology with mammalian C3aRs. Northern blot analysis revealed that the CiC3aR is expressed abundantly in the heart and neural complex and to a lesser extent in the ovaries, hemocytes, and larvae. Three polyclonal Abs raised in rabbits against peptides corresponding to CiC3aR regions of the first and second extracellular loop and of the third intracellular loop react specifically in Western blotting with a single band of 98-102 kDa in hemocyte protein extracts. Immunostaining performed on circulating hemocytes with the three specific Abs revealed that CiC3aR is constitutively expressed only in hyaline and granular amoebocytes. In chemotaxis experiments, the Abs against the first and second extracellular loop inhibited directional migration of hemocytes toward the synthetic peptide reproducing the CiC3a C-terminal sequence, thus providing the compelling evidence that C. intestinalis expresses a functional C3aR homologous to the mammalian receptor. These findings further elucidate the evolutionary origin of the vertebrate complement-mediated proinflammatory process.

Amino Acid Sequence↗
PubMed1998

Effect of soluble complement receptor type 1 on reperfusion edema and neutrophil migration after lung allotransplantation in swine.

OBJECTIVE: Soluble complement receptor type 1 inhibits complement activation by blocking C3 and C5 convertases of the classical and alternative pathways. We evaluated the effect of soluble complement receptor type 1 on lung allograft reperfusion injury. METHODS: Left lung transplantation was performed in 13 weight-matched pigs (25 to 31 kg) after prolonged preservation (20 hours at 1 degree C). One hour after reperfusion the recipient contralateral right lung was excluded to assess graft function only. Complement activity and C3a levels were measured after reperfusion and at the end of the assessment. Extravascular lung water index, intrathoracic blood volume, and cardiac output were assessed during a 5-hour observation period. Gas exchange and hemodynamics were monitored. At the end of the 5-hour assessment period, myeloperoxidase assay and bronchoalveolar lavage were performed to assess neutrophil migration, and C5b-9 (membrane attack complex) deposits in the allograft were detected by immunohistochemistry. Two groups were studied. In group II (n = 6) recipient animals were treated with soluble complement receptor type 1 (15 mg/kg) 15 minutes before reperfusion. Group I (n = 7) served as the control group. RESULTS: Serum complement activity was completely inhibited in group II. In contrast to group I, C5b-9 complexes were not detected in group II allograft tissue samples. C3a was reduced to normal levels in group II (p = 0.00005). Extravascular lung water index was higher in group I animals throughout the assessment period (p = 0.035). No significant difference in allograft myeloperoxidase activity (p = 0.10) and polymorphonuclear leukocyte count of the bronchoalveolar lavage fluid (p = 0.057) was detected. CONCLUSION: Inhibition of the complement system by soluble complement receptor type 1 blocks local complement activation in the allograft and reduces posttransplantation reperfusion edema but does not improve hemodynamic parameters.

Animals↗
PubMed1985

Increased expression of an adhesion-promoting surface glycoprotein in the granulocytopenia of hemodialysis.

To identify the mechanisms accounting for hemodialysis-induced granulocytopenia, we undertook quantitative kinetic studies of a granulocyte-adhesion-promoting surface glycoprotein (Mo1). In eight patients undergoing maintenance hemodialysis, there was a fivefold increase in the mean cell-surface expression of Mo1 within 15 minutes after the start of dialysis with a new cuprophane membrane. The peak increase in surface Mo1 coincided with the maximal drop in neutrophil count and with the peak rise in the plasma levels of the complement-activation products C5a desArg and C3a desArg. During dialysis on a membrane being reused for the fifth time, no significant complement activation, no increase in Mo1 expression, and no change in neutrophil count were seen. C5a desArg (but not C3a desArg) induced a comparable increase in Mo1 expression on normal granulocytes in vitro at concentrations similar to those measured in vivo. Chemotactic peptide-induced granulocyte aggregation (a reflection of increased cell-to-cell adhesiveness) was specifically blocked by mouse monoclonal antibodies to Mo1 in vitro. These data suggest that the increased expression of Mo1 on granulocytes in vivo is in part mediated by C5a (and C5a desArg). The quantitative increase in granulocyte-surface Mo1 may provide a mechanism for initiating leukoaggregation, sequestration of granulocytes, and neutropenia during hemodialysis.

Adult↗
PubMed1993

Changes in levels of anti-dengue virus IgG subclasses in patients with disease of varying severity.

Extensive complement activation precedes onset of shock in dengue patients and complement "split products" C3a and C5a could be responsible, directly or indirectly, for the increased vascular permeability and disseminated intravascular coagulation which characterises dengue haemorrhagic fever (DHF) dengue shock syndrome (DSS). As IgG subclasses vary in their capacity to activate the classical complement pathway after combining with antigen, we have used an indirect enzyme linked immunosorbent assay (ELISA) to assess levels of IgG1-4 against each dengue serotype in acute and convalescent sera from patients with disease of varying severity. Acute phase sera from patients with dengue haemorrhagic fever (DHF) or dengue shock syndrome (DSS) contained higher levels of anti-dengue antibodies of the IgG1, complement fixing, subclass than similar sera from dengue fever (DF) patients. Conversely, acute phase sera from DHF and DSS patients contained lower levels of anti-dengue antibodies of the poor complement activating IgG2 subclass than acute phase sera from DF patients. No significant differences were detected between the levels of anti-dengue IgG3 and IgG4 antibody in acute phase sera from DF, DHF, and DSS patients. With the exception of levels of anti-dengue IgG2 antibody from DHF patients which were lower than those from DF and DSS patients, levels of anti-dengue IgG1, IgG2, IgG3, and IgG4 were similar in convalescent sera from all patients. These results provide a possible explanation for the activation of the serum complement system which precedes onset of shock in severe dengue infections.

Antibodies, Viral↗
PubMed2000

Liposome-induced pulmonary hypertension: properties and mechanism of a complement-mediated pseudoallergic reaction.

Intravenous injection of liposomes can cause significant pulmonary hypertension in pigs, a vasoconstrictive response that provides a sensitive model for the cardiopulmonary distress in humans caused by some liposomal drugs. The reaction was recently shown to be a manifestation of "complement activation-related pseudoallergy" (CARPA; Szebeni J, Fontana JL, Wassef NM, Mongan PD, Morse DS, Dobbins DE, Stahl GL, Bünger R, and Alving CR. Circulation 99: 2302-2309, 1999). In the present study we demonstrate that the composition, size, and administration method of liposomes have significant influence on pulmonary vasoactivity, which varied between instantaneously lethal (following bolus injection of 5 mg lipid) to nondetectable (despite infusion of a 2,000-fold higher dose). Experimental conditions augmenting the pulmonary hypertensive response included the presence of dimyristoyl phosphatidylglycerol, 71 mol% cholesterol, distearoyl phosphatidylcholine, and hemoglobin in liposomes, increased vesicle size and polydispersity, and bolus injection vs. slow infusion. The vasoactivity of large multilamellar liposomes was reproduced with human C3a, C5a, and xenoreactive immunoglobulins, and it correlated with the complement activating and natural antibody binding potential of vesicles. Unilamellar, monodisperse liposomes with 0.19 +/- 0.10 microm mean diameter had no significant vasoactivity. These data indicate that liposome-induced pulmonary hypertension in pigs is multifactorial, it is due to natural antibody-triggered classic pathway complement activation and it can be prevented by appropriate tailoring of the structure and administration method of vesicles.

Animals↗
PubMed1987

Comparison of complement activation by silicone intraocular lenses and polymethylmethacrylate intraocular lenses with polypropylene loops.

Silicone intraocular lenses are undergoing clinical investigation for use in the United States. We compared the ability of silicone intraocular lenses to activate the complement system in human sera with that of polymethylmethacrylate intraocular lenses with polypropylene loops using a radioimmunoassay that measures levels of activated complement fragments. Sera incubated with polymethylmethacrylate lenses with polypropylene loops had higher levels of C3a and C5a, but not C4a, than control sera incubated without intraocular lenses. On the other hand, there were no differences in levels of C3a, C4a, and C5a between sera incubated with silicone lenses and control sera. These results suggest that polymethylmethacrylate lenses with polypropylene loops activate the alternative pathway of complement, while silicone lenses do not.

Complement Activation↗
PubMed2002

Trimellitic anhydride-induced cellular infiltration into Guinea pig lung varies with age but not gender.

BACKGROUND: In humans the incidence of asthma changes with age and gender. Immature guinea pigs have been used to model the allergic response to the occupational allergen trimellitic anhydride (TMA) where exposure to adults is paramount. We hypothesized that the TMA-induced allergic response in immature guinea pigs was similar to mature animals, regardless of gender. METHODS: Sexually immature and mature female and male guinea pigs were sensitized intradermally with TMA. Three weeks after sensitization they were challenged intratracheally with TMA conjugated to guinea pig serum albumin (TMA-GPSA) or GPSA as a control. Twenty-four hours later cell infiltration into the lung was determined. TMA-specific IgG(1) and IgG(2) were measured in plasma and the complement activation product C3a was measured in the bronchoalveolar lavage fluid. RESULTS: In control animals, numbers of eosinophils and neutrophils varied with age and gender. The TMA-GPSA- induced cellular infiltration was similar in all age/gender groups. However, neutrophils in the lung tissue increased only in immature animals. IgG antibodies differed between groups but did not account for differences in cell infiltration. C3a correlated with the extent of cell infiltration in all groups except mature females. CONCLUSIONS: TMA-induced neutrophilia differs with age. TMA-induced changes in eosinophils and macrophages did not vary with age or gender. The relationship between complement activation and inflammation in mature females differs from that in the other groups, suggesting mediators of the response may change with age and gender. Effects of age and gender need to be considered in animal models of the allergic response.

Aging↗
PubMed1993

Cytokine and complement levels in patients undergoing cardiopulmonary bypass.

Patients undergoing cardiopulmonary bypass are known to develop whole body inflammation that often results in a characteristic syndrome early postoperatively. This phenomenon has been attributed to complement activation caused by exposure of blood to the foreign surfaces of the cardiopulmonary bypass circuit. It has been unknown if cytokines are involved. Plasma levels of complement activation products (C3a, C4a, C5a, and C5b-9), interleukins (IL-1 beta, IL-2, IL-4, and IL-6), and tumor necrosis factor-alpha were measured at multiple time points before, during, and after cardiopulmonary bypass in 29 patients. No significant increase over preinduction levels was seen in the cytokines except for IL-6, which was significantly increased during cardiopulmonary bypass (p < 0.001), reaching a maximum 3 hours after cardiopulmonary bypass. C3a, C4a, and C5b-9 levels were significantly elevated during cardiopulmonary bypass (p < 0.001), with maximum C5b-9 levels preceding the IL-6 elevation. Heparin coating of the cardiopulmonary bypass circuit was not demonstrated to have an effect on activation of complement or cytokine production. There was no statistically significant correlation among hemodynamic variables or pulmonary function and complement, interleukin, or tumor necrosis factor-alpha levels. These results confirm the presence of complement activation and demonstrate the production of IL-6 after the generation of C5b-9 in patients undergoing cardiopulmonary bypass. IL-6 may contribute to adverse systemic reactions associated with cardiopulmonary bypass.

Aged↗
PubMed1991

Complement activation in relation to development of preeclampsia.

Six hundred eighty-five primigravidas followed as a series had complement activation evaluated by the formation of anaphylatoxins (C3a and C5a) and terminal C5b-9 complement complexes in venous blood. Samples for complement determinations were obtained four times during pregnancy, in pregnancy weeks 12-16, 20-24, 28-32, and 34-36. Seven of the women developed preeclampsia and one of them the syndrome of hemolysis, elevated liver enzymes, and low platelet count (HELLP syndrome). Eleven others with uncomplicated pregnancies were selected as a control group. Plasma samples were taken from these 18 women at delivery and 1 and 7 days after delivery. At delivery, plasma C5a levels were significantly greater in the preeclamptics than in controls, and four of the seven preeclamptics had elevated plasma C3a values compared with controls. One week after delivery, these plasma anaphylatoxins had returned to normal. Elevations of the anaphylatoxins could not be detected before the women developed clinical signs of preeclampsia. No alterations in terminal C5b-9 complement complexes could be observed in the women with preeclampsia. However, the women who developed HELLP syndrome had elevated plasma concentrations of C3a, C5a, and terminal C5b-9 complement complex at delivery. These values returned to the normal range 1 week after delivery. We conclude that complement activation in the systemic circulation does not occur early in pregnancy and that plasma concentrations of C3a, C5a, or terminal C5b-9 complement complex cannot be used as predictors of preeclampsia.

Adult↗
PubMed1985

Proton nuclear magnetic resonance study of the third component of complement: solution conformation of the carboxyl-terminal segment of C3a fragment.

A proton nuclear magnetic resonance (NMR) study is reported of des-Arg-C3a, which is a 76-residue fragment obtained from the N-terminal portion of the alpha chain of the third component of human complement. A method of carboxypeptidase digestion/difference spectroscopy [Endo, S., & Arata, Y. (1985) Biochemistry 24, 1561-1568] was used for the spectral assignments for Ala-76, Leu-75, Gly-74, His-72, His-67, and Ala-48. On the basis of the NMR results obtained for these residues, we conclude that in aqueous solution (1) the C-terminal segment Leu-73-Ala-76 is free from interactions with the rest of the C3a molecule and (2) the major part of the C-terminal segment takes an ordered conformation. We also suggest that the presence of a core, which is formed by segment Tyr-15-Tyr-59 [Huber, R., Scholze, H., Paques, E. P., & Deisenhofer, J. (1980) Hoppe-Seyler's Z. Physiol. Chem. 361, 1389-1399], is essential for the C-terminal segment in maintaining the ordered structure in aqueous solution. 1H NMR spectral data were also obtained for the intact C3 from human and porcine sources. The resonances for the C2-H protons of His-67 and His-72, which exist in the C3a part of the human C3 molecule, were assigned. Comparisons of the results obtained with those for des-Arg-C3a demonstrate that upon cleavage of C3a very little change, if any, is induced in microenvironments of His-67 and His-72 and a piece of segment that contains His-72 is exposed to solvent and highly flexible.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1984

Activated complement in inflamed aqueous humor.

Activated complement is an important mediator of inflammation. Radioimmunoassay was used to measure levels of C3a, an activated fragment of C3, in aqueous humor. Additionally, immunoelectrophoresis was performed on aqueous humor to detect Factor B and its conversion product, Bb, as well as C3c, a breakdown product of C3. All six samples of normal aqueous humor had no detectable C3a, C3c, or Factor B. All eight samples of aqueous humor from patients with anterior uveitis had measurable levels of C3a. Factor B and C3c were detected in 3/7 samples of inflamed aqueous humor. Factor B was converted fully to Bb in two of these three samples, suggesting alternative pathway activation of complement. Activated complement fragments are present in the aqueous humor of eyes with anterior uveitis and may help mediate the inflammatory process.

Adult↗
PubMed1988

Inhibition of complement activation by high-dose corticosteroids in total hip arthroplasty.

Anaphylatoxins are released during total hip arthroplasties (THA) when methylmethacrylate is used. These toxins may be responsible for hemodynamic and pulmonary instability during surgery. Recent studies have shown that the release of anaphylatoxins may be inhibited by high-dose corticosteroids (HDC). In a double-blind study 30 consecutive patients with osteoarthritis or failed hip fractures were randomized into two groups; 15 patients received HDC at the beginning of the operation and 15 patients, designated the control group, received infused saline. Anaphylatoxin formation, arterial oxygen tension, and blood pressure were determined preoperatively, during the operation, and one day postoperatively. The patients who received HDC had no significant alteration regarding the anaphylatoxins or arterial oxygen tension during surgery. However, in the control group elevated C3a levels and decreased PaO2 levels were found. Corticosteroids therefore inhibit complement activation and anaphylatoxin release in hip arthroplasty surgery.

Aged↗
PubMed1991

Complement is activated in the upper respiratory tract during influenza virus infection.

The purpose of this pilot study was to determine whether complement is activated in the upper respiratory tract during experimental influenza virus infection in human volunteers. Seven subjects were challenged with influenza A/Bethesda/1/85 (H3N2), and four subjects received placebo. C3a and C5a concentrations were measured by radioimmunoassay in nasal lavage fluids before challenge and for 8 days after challenge. A significant increase (p less than 0.05) in C3a and C5a concentrations was demonstrated in lavage fluids from subjects who developed influenza illness as compared with uninfected control subjects and infected subjects who remained asymptomatic. Maximal levels of C3a and C5a were detected during the recovery phase of illness. These results suggest that complement is activated in the airway in response to influenza illness.

Adult↗
PubMed2005

A randomized, placebo-controlled trial of complement inhibition in ischemia-reperfusion injury after lung transplantation in human beings.

OBJECTIVE: Complement activation has been shown to play a significant role in ischemia-reperfusion injury after lung transplantation. TP-10 (soluble complement receptor 1 inhibitor) inhibits the activation of complement by inactivating C3a and C5a convertases. This was a clinical trial of TP-10 to reduce ischemia-reperfusion injury in lung transplantation. METHODS: In a randomized, double-blinded, multicenter, placebo-controlled trial, 59 patients from four lung transplant programs received TP-10 (10 mg/kg, n = 28) or placebo (n = 31) before reperfusion. This dose achieved 90% complement inhibition for 24 hours, and activity had returned toward normal by 72 hours. RESULTS: At 24 hours, 14 of 28 patients in the TP-10 group (50%) were extubated, whereas only 6 of 31 patients in the placebo group (19%) were (P = .01). The total times on the ventilator and in the intensive care unit both tended to be shorter in the TP-10 group, but these differences did not achieve statistical significance. Among patients requiring cardiopulmonary bypass (n = 5 in placebo group and n = 7 in TP-10 group), the mean duration of mechanical ventilation was reduced by 11 days in the TP-10 group (10.6 +/- 5.0 days vs 21.5 +/- 5.9 days in placebo group, P = .2). Operative deaths, incidences of infection and rejection, and length of hospital stay were not significantly different between the two groups. CONCLUSIONS: Short-term complement inhibition with TP-10 led to early extubation in a significantly higher proportion of lung transplant recipients. The effect of TP-10 was greater among patients undergoing cardiopulmonary bypass, with a large reduction in ventilator days. Complement inhibition thus significantly decreases the duration of mechanical ventilation and could be useful in improving the outcome of lung transplant recipients.

Adolescent↗
PubMed2004

The anaphylatoxins bridge innate and adaptive immune responses in allergic asthma.

The complement system has long been recognized for its role as a lytic effector system that protects against microbial pathogens, as well as for its role in mediating acute and chronic inflammatory responses. Many of the inflammatory sequelae of complement activation can be related to the complement cleavage fragments C3a and C5a, the so-called anaphylatoxins (ATs). Cloning and subsequent gene targeting of their corresponding receptors, as well as generation of specific C3a and C5a inhibitors, have fueled new interest in studies aimed at defining the roles of the anaphylatoxins in inflammatory diseases. Traditionally, the anaphylatoxins have been considered mediators of end-stage effector mechanisms. However, recent data from animal models of allergic asthma suggest that C3a and C5a provide a critical link between innate and adaptive immunity. This review is aimed at outlining our current knowledge of when and where anaphylatoxins contribute to and control the development of allergic asthma. The accumulated data suggest a model in which C3a and C5a play important but opposing roles during allergen-induced T-cell polarization: C3a promotes Th2 responses, whereas C5a prevents Th2 polarization. During the effector phase, both anaphylatoxins trigger the inflammatory response and contribute to bronchoconstriction.

Allergens↗