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PubMed2002

Role of complement in tubulointerstitial injury from proteinuria.

The complement system is being increasingly implicated in the pathogenesis of progressive renal disease resulting from persistent proteinuria. It has recently been established that renal tubular cells can produce complement, activate complement, and respond to complement activation. Complement proteins that pass through the glomerular barrier along with other serum proteins in the proteinuric state may become activated at the tubular epithelial brush border, and lead to a cascade of events culminating in cell injury. Furthermore, nephrotic components in the urinary space may cause direct activation of the tubular cells to overexpress complement and contribute to local tissue injury. In this review, we will discuss the current evidence supporting a role for complement in the pathogenesis of progressive tubulointerstitial damage in the proteinuric state. The possibility of complement inhibition intervening in progressive tubulointerstitial injury due to proteinuric glomerular disease will also be considered.

Complement System Proteins↗
PubMed1988

Leukocytes, eosinophils and complement function during hemodialysis with polysulphone and polymethylmethacrylate membranes: comparison with cuprophan and polyacrylonitrile.

The biocompatibility of the two new dialysis membranes, polysulphone (PS) and polymethylmethacrylate (PMMA), was evaluated versus cuprophan (CUP) and polyacrylonitrile (PAN) by studying the in vivo effects of the four different membranes on leukocyte counts, eosinophil levels and complement function both in the presence and absence of dialysis fluid. Complement function was also examined in vitro by studying the generation of chemotactic factors, whole complement activity and C3d serum conversion. Passive absorption of complement fractions by membranes has completed in vitro studies. PS, PMMA and PAN showed a higher biocompatibility than CUP, even if slight differences can be observed: PS showed a PAN-like biocompatibility pattern with a relatively high absorption of complement factors by the membrane and without complement activation. On the other hand, PMMA showed a CUP-like pattern and caused complement activation, even though to a lower intensity than CUP. PMMA biocompatibility appears to stand in-between CUP and the other two synthetic membranes PS and PAN. Our results confirm the important role played by membrane-induced complement activation on hemodialysis leukopenia. Dialysis fluid does not have a significant influence on membrane biocompatibility, but represents the major factor in determining intradialytic eosinopenia. Eosinophils seem to represent a more important marker of dialysis than of membrane biocompatibility.

Acrylic Resins↗
PubMed1976

Fc- and complement-receptor rosette-forming cell ratios in human tonsils and peripheral blood.

Lymphocytes were investigated for both Fc- and complement-rosette-forming cell activities. At least three subpopulations differing in the relative activities of the Fc and complement receptors have been disclosed. In human tonsils a subpopulation of B lymphocytes had a higher complement-receptor activity than Fc-receptor activity. In contrast, the peripheral cells from a patient with a lymphoma and another with an undiagnosed lymphocytic disease contained a population of B lymphocytes with higher Fc-receptor than complement- receptor activity. In three patients with chronic lymphocytic leukemia, B lymphocytes contained both Fc- and complement-receptor activities. No differences between complement- and Fc-receptor activities were evident in normal human peripheral blood. Fc-receptor, but not complement-receptor activity was inhibited by 2% gamma-globulin, or 8 X 10(3) M iodoacetate. EDTA at 1.7 X 19(-2) M concentration has no effect upon Fc- or complement-rosette-forming cells. The activity of both receptors was diminished at 4 degrees C.

B-Lymphocytes↗
PubMed1985

Kinetic study of rheumatoid factor influence on complement-mediated modulation of immune precipitation.

Human monoclonal IgM kappa rheumatoid factor PA (mRF) expressed various effects on complement-dependent modulation of ovalbumin/antiovalbumin lattice formation measured kinetically by laser light scattering (LLS): (1) in the absence of complement, mRF (44.2-177 U/ml) caused enhancement of LLS in a dose-dependent manner; (2) mRF partially prevented expression of complement-mediated inhibition of lattice formation and, at the same time, complement inhibits mRF-dependent LLS enhancement; (3) complement caused disruption of lattice-mRF bonds during solubilization of preformed lattice-mRF complex as demonstrated by specific mRF activity in supernatants. This effect is dependent on complement activity and on both complement and mRF concentrations; (4) ovalbumin/antiovalbumin complexes gradually lost the ability to react with mRF during the first 2 min of complement-mediated inhibition of lattice formation.

Antibodies, Monoclonal↗
PubMed1998

C-reactive protein frequently colocalizes with the terminal complement complex in the intima of early atherosclerotic lesions of human coronary arteries.

There is increasing evidence that complement activation may play a role in atherogenesis. Complement proteins have been demonstrated to be present in early atherosclerotic lesions of animals and humans, and cholesterol-induced atherosclerotic lesion formation is reduced in complement-deficient animals. Potential complement activators in atherosclerotic lesions are now a subject matter of debate. C-reactive protein (CRP) is an acute-phase protein that is involved in inflammatory processes in numerous ways. It binds to lipoproteins and activates the complement system via the classic pathway. In this study we have investigated early atherosclerotic lesions of human coronary arteries by means of immunohistochemical staining. We demonstrate here that CRP deposits in the arterial wall in early atherosclerotic lesions with 2 predominant manifestations. First, there is a diffuse rather than a focal deposition in the deep fibroelastic layer and in the fibromuscular layer of the intima adjacent to the media. In this location, CRP frequently colocalizes with the terminal complement complex. Second, the majority of foam cells below the endothelium show positive staining for CRP. In this location, no colocalization with the terminal complement proteins can be observed. Our data suggest that CRP may promote atherosclerotic lesion formation by activating the complement system and being involved in foam cell formation.

Animals↗
PubMed2003

Mechanism of complement activation and its role in the inflammatory response after thoracoabdominal aortic aneurysm repair.

BACKGROUND: Complement activation contributes to ischemia-reperfusion injury. Patients undergoing thoracoabdominal aortic aneurysm (TAAA) repair suffer extensive ischemia-reperfusion and considerable systemic inflammation. METHODS AND RESULTS: The degree and mechanism of complement activation and its role in inflammation were investigated in 19 patients undergoing TAAA repair. Patients undergoing open infrarenal aortic surgery (n=5) or endovascular descending aortic aneurysm repair (n=6) served as control subjects. Substantial complement activation was seen in TAAA patients but not in controls. C1rs-C1-inhibitor complexes increased moderately, whereas C4bc, C3bBbP, C3bc, and the terminal SC5b-9 complex (TCC) increased markedly after reperfusion, reaching a maximum 8 hours after reperfusion. Interleukin (IL)-1beta, tumor necrosis factor alpha (TNF-alpha), and IL-8 increased significantly in TAAA patients but not in controls, peaking at 24 hours postoperatively and correlating closely with the degree of complement activation. IL-6 and IL-10 increased to a maximum 8 hours after reperfusion in the TAAA patients, were not correlated with complement activation, and increased moderately in the control subjects. Myeloperoxidase and lactoferrin increased markedly before reperfusion in all groups, whereas sICAM-1, sP-selectin, and sE-selectin were unchanged. No increase was observed in complement activation products, IL-1beta, TNF-alpha, or IL-8 in a mannose-binding lectin (MBL)-deficient TAAA patient, whereas IL-6, IL-10, myeloperoxidase, and lactoferrin increased as in the controls. Two other MBL-deficient TAAA patients receiving plasma attained significant MBL levels and showed complement and cytokine patterns identical to the MBL-sufficient TAAA patients. CONCLUSIONS: The data suggest that complement activation during TAAA repair is MBL mediated, amplified through the alternative pathway, and responsible in part for the inflammatory response.

Aged↗
PubMed2006

Inhibition of complement component C3 reduces vein graft atherosclerosis in apolipoprotein E3-Leiden transgenic mice.

BACKGROUND: Venous bypass grafts may fail because of development of intimal hyperplasia and accelerated atherosclerosis. Inflammation plays a major role in these processes. Complement is an important part of the immune system and participates in the regulation of inflammation. The exact role of complement in the process of accelerated atherosclerosis of vein grafts has not yet been explored, however. METHODS AND RESULTS: To assess the role of complement in the development of vein graft atherosclerosis, a mouse model, in which a venous interposition was placed in the common carotid artery, was used. In this model, vein graft thickening appeared within 4 weeks. The expression of complement components was studied with the use of immunohistochemistry on sections of the thickened vein graft. C1q, C3, C9, and the regulatory proteins CD59 and complement receptor-related gene y could be detected in the lesions 4 weeks after surgery. Quantitative mRNA analysis for C1q, C3, CD59, and complement receptor-related gene y revealed expression of these molecules in the thickened vein graft, whereas C9 did not show local mRNA expression. Furthermore, interference with C3 activation with complement receptor-related gene y-Ig was associated with reduced vein graft thickening, reduced C3 and C9 deposition, and reduced inflammation as assessed by analysis of influx of inflammatory cells, such as leukocytes, T cells, and monocytes. In addition, changes in apoptosis and proliferation were observed. When C3 was inhibited by cobra venom factor, a similar reduction in vein graft thickening was observed. CONCLUSIONS: The complement cascade is involved in vein graft thickening and may be a target for therapy in vein graft failure disease.

Animals↗
PubMed1974

The roles of IgG, IgM rheumatoid factor, and their complexes in the induction of polymorphonuclear leukocyte chemotactic factor from complement.

The induction of chemotactic factor by rheumatoid factor (RF) and by rheumatoid complexes and their constituents was investigated. The presence of chemotactic factor was measured by the number of polymorphonuclear leukocytes (obtained from normal individuals) attracted through a 3 mum Millipore filter and is expressed as a "chemotactic index." The chemotactic index was used to measure the effect of immunoglobulins and their complexes in stimulating production of complement-derived chemotactic factors from the sera of normal individuals. Two sources of IgG (F-II and DEAE-purified IgG) were used. These were prepared for use in the native and heat-aggregated states. The same chemotactic index was obtained with both these preparations of IgG. The chemotactic index increases when (a) increasing concentrations of gamma globulin were added to a constant concentration of complement and (b) when the amount of complement alone was increased. The addition of a purified IgM RF to the mixture of IgG and complement caused a decrease in the chemotactic index. Incubation of IgG and complement before addition of IgM RF produced no change in the chemotactic index. The addition of a nonrheumatoid factor IgM to IgM and complement had no effect on the chemotactic index. IgM RF and IgG alone were not chemotactic. These studies confirm the concept of "complement deviation" by IgM RF which occurs with, and as a result of, the immune complex formation between IgG and IgM RF. The successful activation of complement chemotactic factors by IgG may explain the synovitis with high polymorphonuclear leukocyte counts found in RF-negative arthritis.

Antigen-Antibody Complex↗
PubMed1975

Alteration of human erythrocyte membrane properties by complement fixation.

Erythrocyte survival studies of complement-coated radiolabeled erythrocytes have shown rapid removal of these cells from the peripheral blood with a return of these cells into the circulation within a few hours. We studied complement-coated human erythrocytes and measured surface charge and deformability, two parameters believed to be important in erythrocyte survival. Erythrocytes were coated with complement by two in vitro techniques: the addition of (a) low ionic strength sucrose, and (b) IgM cold agglutinins. Erythrocytes obtained from three patients with cold agglutinin disease were used as a source of in vivo complement-coated cells. No difference was found in surface charge as measured by electrophoretic mobility between erythrocytes from normal subjects and complement-coated erythrocytes from any of the three sources. When deformability was measured by filtration through 3-mum polycarbonate sieves, marked decreases in deformability were found in complement-coated erythrocytes. The filtration returned toward control levels by incubating the complement-coated erythrocytes in serum for 1 h and correlated with decreases in immune adherence. Using screen filtration pressure as a measure of deformability, a positive correlation between number of C3 molecules per erythrocyte and decreased deformability was found. C3b appeared responsible for the decreased deformability of the erythrocytes, since conversion of C3b to C3d resulted in a return of deformability toward normal. The data suggested that the sequestration of complement-coated human erythrocytes in the microvasculature can be explained in part by decreased deformability and changes in immune adherence.

Agglutinins↗
PubMed1978

The acute effects of antiglomerular basement membrane antibody upon glomerular filtration in the rat. The influence of dose and complement depletion.

Recent studies from this laboratory have revealed that single nephron filtration rate (sngfr) decreases significantly within 1 h of the administration of large doses of complement-fixing antiglomerular basement membrane antibody (AGBM Ab) in plasma-expanded Munich-Wistar rats. This reduction in sngfr was due to decreases in nephron plasma flow (rf) and the glomerular permeability coefficient (LpA) utilizing direct evaluation of all pertinent pressures, flows, and permeabilities. With identical micropuncture techniques, we have determined (a) the respective influences of rpf and LpA upon sngfr by examining the effects of differing doses of AGBM Ab, and (b) the specific effect of complement fixation upon the reduction in sngfr. In normal rats, low dose (1.4 microgram/g body wt) AGBM Ab decreased sngfr from 57.9 +/- 3.4 to 50.8+/- 3.9 nl/min per g kidney wt (kw) (P less than 0.001), and this was due to a 10% reduction in rpf and a decrease in LpA FROM 0.069 +/- 0.014 in control to 0.041 +/- 0.007 nl/s per g kw per mm Hg (P less than 0.02). At the high dose (2.3 microgram/g body wt), sngfr fell dramatically from 58.4 +/- 4.0 to 7.6 +/- 3.8 nl/min per g kw (P less than 0.001), and this effect upon filtration was the result of an 86% reduction in rpf and a decrease in LpA from 0.092 +/- 0.020 to 0.007 +/- 0.004 nl/s per g kw mm Hg (P less than 0.001). Therefore, at lower doses sngfr fell primarily as a result of a 40% reduction in LpA and a 10% decrease in rpf; however, at the high dose massive reductions in both rps and LpA led to the large decrease in sngfr. In complement-depleted rats, receiving identical doses, low-dose AGBM Ab no longer reduced the sngfr, but a reduction in LpA persisted (other factors compensating to maintain sngfr). At the high dose, complement depletion ameliorated the reduction in sngfr (55.1 +/- 2.4 to 37.2 +/- 3.4 nl/min per g kw mm Hg) by nearly eliminating the vasoconstriction but only partially diminished the reduction in LpA (0.097 +/- 0.020 to 0.032 +/- 0.004 nl/s per g kw mm Hg, P less than 0.05). Complement depletion prevented the migration of polymorphonuclear leukocytes (present in larger numbers after the high dose of AGBM Ab) into the capillary and eliminated vasoconstriction. Complement depletion resulted in a lesser effect of high-dose AGBM Ab upon LpA than in normal rats, and this is likely due to lesser polymorphonuclear leukocyte effects upon capillary surface area. The persistent reduction in LpA observed in complement-depleted rats correlated with separation of the endothelial cell from the glomerular basement membrane after AGBM Ab, AGBM Ab diminished glomerular ultrafiltration by decreasing LpA and altering the endothelial surface of the glomerular membrane, and this effect is not totally dependent upon the fixation of complement.

Animals↗
PubMed1988

Decay-accelerating factor protects human tumor cells from complement-mediated cytotoxicity in vitro.

The disialoganglioside GD2 is expressed on a wide spectrum of human tumor types, including neuroblastomas and melanomas. Upon binding of 3F8, a murine monoclonal antibody (MAb) specific for GD2, neuroblastomas and some melanomas are sensitive to killing by human complement, whereas some melanomas are not. To investigate the mechanism underlying these differences in complement mediated cytotoxicity, complement-insensitive melanoma cell lines were compared with respect to expression of the decay-accelerating factor (DAF), a membrane regulatory protein that protects blood cells from autologous complement attack. While DAF was undetectable among neuroblastomas, it was present in complement-insensitive melanomas. When the function of DAF was blocked by anti-DAF MAb, C3 uptake and complement-mediated lysis of the insensitive melanoma lines were markedly enhanced. F(ab')2 fragments were as effective in enhancing lysis as intact anti-DAF MAb. The DAF-negative and DAF-positive melanoma cell lines were comparably resistant to passive lysis by cobra venom factor-treated serum. The data suggest that in some tumors, DAF activity accounts for their resistance to complement-mediated killing. The ability to render these cells complement-sensitive by blocking DAF function may have implications for immunotherapy.

Antibodies, Monoclonal↗
PubMed2001

Expression of complement inhibitors CD46, CD55, and CD59 on tumor cells does not predict clinical outcome after rituximab treatment in follicular non-Hodgkin lymphoma.

Rituximab is a chimeric monoclonal antibody that targets B-cell-specific antigen CD20 and an effective treatment for B-cell non-Hodgkin lymphoma. Although it is readily used in clinical practice, the exact mechanism of its antitumor effect is unclear. One potential mechanism involves complement-mediated cytotoxicity. It has been shown that rituximab induces complement-mediated cytotoxicity in follicular lymphoma cells in vitro, and complement inhibitors CD55 and CD59 may regulate this process. To determine whether complement inhibitors play a role in regulating the antitumor effect of rituximab, the expression of complement inhibitors CD46, CD55, and CD59 was analyzed in pretreatment tumor cells from 29 rituximab-treated follicular lymphoma patients. Among them, 8 patients achieved complete responses, 11 patients achieved partial responses, and 10 patients showed no or minimal responses to rituximab treatment. Expression of surface CD20, CD46, CD55, and CD59 was determined by 2-color flow cytometry. Although the CD59 level was slightly lower in the complete response group, there was no statistically significant difference in the expression of individual complement inhibitor CD46 (mean channel fluorescence [MCF]: NR, 26.4; PR, 21.9; CR, 29.9), CD55 (MCF: NR, 16.4; PR, 14.9; CR, 23.2), or CD59 (MCF: NR, 41.6; PR, 40.6; CR, 30.6), the combination of any 2 inhibitors, or all 3 on tumor cells from 3 response groups. In addition, there was no difference in the rituximab-induced complement-mediated cytotoxicity in an in vitro assay using tumor cells from 3 response groups. Thus, CD46, CD55, and CD59 expression on pretreatment tumor cells, or their susceptibility to in vitro complement-mediated killing, does not predict clinical outcome after rituximab treatment.

Adult↗
PubMed2005

Herbal complement inhibitors in the treatment of neuroinflammation: future strategy for neuroprotection.

The upregulated complement system plays a damaging role in disorders of the central nervous system (CNS). The classical and alternate pathways are two major pathways activated in neuroinflammatory disorders such as Alzheimer's disease, multiple sclerosis, traumatic brain injury, spinal cord injury, HIV-associated dementia, Parkinson's disease, and mad cow disease. Failure of currently available anti-inflammatory agents, especially cyclooxygenase inhibitors, in offering significant neuroprotection in large epidemiologic clinical trials of CNS disorders suggests an urgent need for the development of new neuroprotective agents. The positive preclinical outcomes in treating CNS disorders by complement regulatory molecules, such as vaccinia virus complement control protein, suggest the possibility of using complement-inhibitory molecules as neuroprotective agents. Several active ingredients of herbal origin are found to have complement-inhibitory activity. These herbal ingredients along with other anti-inflammatory roles might be useful in treating neuroinflammation associated with CNS disorders. Active ingredients of herbal origin with complement inhibitory ingredients are summarized and classified according to their chemical nature and specificity towards the major pathways activating the complement system. The structure activity relationship of some specific examples is also discussed in this report. This information might be helpful in formulating a natural panacea against complement-mediated neuroinflammation.

Complement Inactivating Agents↗
PubMed2004

CR1-based inhibitors for prevention of complement-mediated immune hemolysis.

Complement receptor 1 (CR1) is a single pass transmembrane glycoprotein that, through its ability to bind key components of the complement cascade, can inhibit both the classical and alternative pathways. Using several animal models, a recombinant form of CR1 has been documented to be effective in reducing tissue damage that occurs as a result of complement activation in various inflammatory conditions. This strategy is currently being explored in human clinical trials. Activation of complement cascade via the antibody-mediated classical pathway can initiate red blood cell destruction, causing transfusion reactions and hemolytic anemia. We discuss here our approach of using CR1 derivatives as therapeutic targets for prevention of complement-dependent immune hemolysis. Using a mouse model of hemolytic transfusion reaction, we have found that sCR1 treatment reduces complement activation and prolongs the survival of transfused red blood cells. Through structure-function analysis, we have identified a complement inhibitory domain located at the amino-terminal region of CR1 that mediates its antihemolytic activity in vivo. Collectively, our data highlight a potential use for CR1 to control complement-dependent immune hemolysis and identify its functional domains for the future design of CR1-based inhibitors.

Anemia, Hemolytic↗
PubMed2006

Activation of kainate receptors sensitizes oligodendrocytes to complement attack.

Glutamate excitotoxicity and complement attack have both been implicated separately in the generation of tissue damage in multiple sclerosis and in its animal model, experimental autoimmune encephalomyelitis. Here, we investigated whether glutamate receptor activation sensitizes oligodendrocytes to complement attack. We found that a brief incubation with glutamate followed by exposure to complement was lethal to oligodendrocytes in vitro and in freshly isolated optic nerves. Complement toxicity was induced by activation of kainate but not of AMPA receptors and was abolished by removing calcium from the medium during glutamate priming. Dose-response studies showed that sensitization to complement attack is induced by two distinct kainate receptor populations displaying high and low affinities for glutamate. Oligodendrocyte death by complement required the formation of the membrane attack complex, which in turn increased membrane conductance and induced calcium overload and mitochondrial depolarization as well as a rise in the level of reactive oxygen species. Treatment with the antioxidant Trolox and inhibition of poly(ADP-ribose) polymerase-1, but not of caspases, protected oligodendrocytes against damage induced by complement. These findings indicate that glutamate sensitization of oligodendrocytes to complement attack may contribute to white matter damage in acute and chronic neurological disorders.

Animals↗
PubMed1996

Complement synthesis in the injured kidney: does it have a role in immune complex glomerulonephritis?

On pages 2428 to 2433 of this issue, Miyazaki et al. provide evidence that complement component C3 is synthesized within the glomeruli of patients with mesangial glomerulonephritis. Although it has been known for several years that cells isolated from the human kidney can synthesize a range of complement components, and that immune complex disease can increase the expression of these genes, it is only now that the link between intraglomerular synthesis of complement and human glomerulonephritis can be made. In view of the long interest in the role of complement in the pathogenesis of glomerulonephritis, this begs the question to what extent local complement synthesis may be involved in the generation of tissue injury. Given also the double-sided nature of complement-proinflammatory and protective-It remains to be seen if the roles of local and systemic complement differ in these respects. To weigh these questions, we examine the current evidence that connects local complement synthesis with renal injury, and ask what studies are needed to provide more definitive answers.

Animals↗
PubMedDate not supplied

Complement-inhibiting activity of human seminal plasma and semen quality.

Human seminal plasma (SP) contains potent complement inhibitors. This study examined the complement-inhibiting activity of individual SP samples from 118 patients with infertility and analyzed them in relation to various semen parameters. When 25% complement-inhibiting activity was considered the cut off value, less than 1 SD unit from the mean percentage of inhibition of SP samples with normal semen quality, 32 samples (27%) showed low inhibiting activity. Among the lower group, incidences of patients with asthenozoospermia (66%) and oligozoospermia (31%) were significantly (p < .01) higher than those (36 and 10%) in the group whose SP showed significant inhibiting activity. Partial characterization revealed that the component responsible for complement inhibition was heat labile, trypsin resistant, high molecular weight (>10 kD) glycoprotein that can inhibit alternative as well as classical complement pathways. Furthermore, since in the majority of SP samples the anticomplementary activity was blocked by monoclonal antibody against membrane cofactor protein (MCP) or decay accelerating factor (DAF), the complement-inhibiting factors that were identified are likely to be MCP and/or DAF, which are known to be present in human SP. These results suggest that complement-regulatory proteins in SP such as MCP and DAF may protect sperm cells against complement attack in the male reproductive tract.

Complement Inactivator Proteins↗
PubMed2005

Effect of IL-4 on altered expression of complement activation regulators in rat pancreatic cells during severe acute pancreatitis.

AIM: To investigate the effect of IL-4 on the altered expression of complement activation regulators in pancreas and pancreatic necrosis during experimental severe acute pancreatitis (SAP). METHODS: SAP model of rats was established by retrograde injection of 5% sodium taurocholate (1 mL/kg) into the pancreatic duct. We immunohistochemically assayed the expression of three complement activation regulators: decay accelerating factor (DAF; CD55), 20 ku homologous restriction factor (HRF20; CD59) and membrane cofactor protein (MCP; CD46), in the pancreatic acinar cells of rats at 0, 3, 6, 12, and 24 h after the induction of SAP model. Meanwhile the levels of amylase and lipase were determined, and morphological examination was performed. Then, 61 rats were randomly divided into three groups. Group A (n=21) received no treatment after the SAP model was established; group B (n=20) was given IL-4 (8 microg/animal) intraperitoneally 0.5 h before the SAP model was established; group C (n=20) was given IL-4 (8 microg/animal) intraperitoneally 0.5 h after the SAP model was established. Plasma amylase and lipase, extent of pancreatic necrosis and expression of complement activation regulators were investigated 6 h after the induction of SAP model. RESULTS: Three complement activation regulators were all expressed in pancreatic acinar cells. MCP was not found on the basolateral surface as reported. Contrary to the gradually increasing plasma level of amylase and lipase, expression of complement activation regulators decreased after SAP model was set up. At the same time, the severity of pancreatic necrosis was enhanced. A strong negative correlation was found between the expression of MCP, DAF, CD59 in pancreatic acinar cells and the severity of pancreatic necrosis (r= -0.748, -0.827, -0.723; P<0.01). In the second series of experiments, no matter when the treatment of IL-4 was given (before or after the induction of SAP model), the serum level of amylase or lipase was decreased and the extent of pancreatic necrosis was ameliorated significantly. Compared to SAP control group, the expression of DAF and CD59 in pancreas was reinforced when IL-4 was given before the induction of SAP model (P<0.01, P<0.05), but the expression of MCP was not influenced (P>0.05). The expression of DAF was enhanced, when IL-4 was given after the induction of SAP model (P<0.05), but the expression of CD59 and MCP did not change (P>0.05). CONCLUSION: Complement activation regulators may participate in the pathogenesis of pancreatic inflammation. Downregulation of complement activation regulators expression may be one of the causes of pancreatic necrosis. IL-4 treatment may control SAP aggravation by enhancing expression of DAF and CD59 in pancreas and decreasing pancreatic necrosis. Moreover, DAF and CD59 may play an important role in the regulation of complement activation regulators during SAP.

Animals↗