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Results for “Complement Membrane Attack Complex”

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At least 1,369 records · Page 76Linked to original sources
PubMed1998

CD59 protects glomerular endothelial cells from immune-mediated thrombotic microangiopathy in rats.

CD59 is a cell membrane-bound complement regulatory protein on glomerular cells that inhibits C5b-9 assembly and insertion. This report describes a recently developed model of immune thrombotic microangiopathy (TMA) induced by the renal artery perfusion of anti-glomerular endothelial cell (anti-GEN) antibody. To examine the role of CD59 in protecting the GEN from immune-mediated injury, rats underwent selective renal artery perfusion with F(ab')2 fragments of anti-CD59 monoclonal antibody to block CD59 activity or control mouse IgG followed by anti-GEN antibody or control goat IgG. Neutralization of CD59 in normal rats did not result in any significant functional or histologic changes. Perfusion with anti-CD59 did not change deposition of the pathogenic anti-GEN IgG used to induce the TMA model. However, neutralization of CD59 in the TMA model resulted in more C5b-9 formation in glomeruli, accompanied by increased platelet and fibrin deposition, more severe endothelial injury, and reduced renal function compared with the animals perfused with control F(ab')2 fragments. These results demonstrate directly that CD59 serves a protective role for GEN in this TMA model of rats, and confirm that C5b-9 formation has a critical pathogenic role in the mediation of the disease. CD59 may play an important role in protecting glomerular endothelium from other complement-mediated types of injury.

Animals↗
PubMed2004

Mechanisms of tubulointerstitial injury in the kidney: final common pathways to end-stage renal failure.

There are many different glomerular disorders, including glomerulonephritis, diabetic nephropathy, and hypertensive nephrosclerosis. However, once glomerular damage reaches a certain threshold, the progression of renal disease is consistent and irreversible. Recent studies emphasized the crucial role of tubulointerstitial injury as a mediator of progression of kidney disease. One common mechanism that leads to renal failure via tubulointerstitial injury is massive proteinuria. Accumulating evidence suggests critical effects of filtered macromolecules on tubular cells, including lysosomal rupture, energy depletion, and tubular injury directly induced by specific components such as complement components. Another common mechanism is chronic hypoxia in the tubulointerstitium. Tubulointerstitial damage results in the loss of peritubular capillaries, impairing blood flow delivery. Interstitial fibrosis also impairs oxygen diffusion and supply to tubular cells. This induces chronic hypoxia in this compartment, rendering a vicious cycle. Development of novel therapeutic approaches against these final common pathways will enable us to target any types of renal disease.

Adult↗
PubMed2002

Complement activates the c-Jun N-terminal kinase/stress-activated protein kinase in glomerular epithelial cells.

In the rat passive Heymann nephritis model of membranous nephropathy, complement C5b-9 induces sublethal glomerular epithelial cell (GEC) injury and proteinuria. C5b-9 activates cytosolic phospholipase A(2) (cPLA(2)), and products of cPLA(2)-mediated phospholipid hydrolysis modulate GEC injury and proteinuria. In the present study, we demonstrate that C5b-9 activates c-Jun N-terminal kinase (JNK) in cultured rat GECs and that JNK activity is increased in glomeruli isolated from proteinuric rats with passive Heymann nephritis, as compared with control rats. Stable overexpression of cPLA(2) in GECs amplified complement-induced release of arachidonic acid (AA) and JNK activity, as compared with neo (control) GECs. Activation of JNK was not affected by indomethacin. Incubation of GECs with complement stimulated production of superoxide, and pretreatment with the antioxidants, N-acetylcysteine, glutathione, and alpha-tocopherol as well as with diphenylene iodonium, an inhibitor of the NADPH oxidase, inhibited complement-induced JNK activation. Conversely, H(2)O(2) activated JNK, whereas exogenously added AA stimulated both superoxide production and JNK activity. Overexpression of a dominant-inhibitory JNK mutant or treatment with diphenylene iodonium exacerbated complement-dependent GEC injury. Thus, activation of cPLA(2) and release of AA facilitate complement-induced JNK activation. AA may activate the NADPH oxidase, leading to production of reactive oxygen species, which in turn mediate the activation of JNK. The functional role of JNK activation is to limit or protect GECs from complement attack.

Animals↗
PubMed1999

[Clinical features of meningococcal infection in subjects with deficient terminal components of complement].

AIM: To evaluate clinical characteristics of meningococcal disease (MD) in individuals with terminal complement component deficiency (TCCD) who are thousands times more susceptible to MD than complement-sufficient persons. MATERIALS AND METHODS: 61 cases of MD in TCCD patients and 200 randomly selected cases of MD in complement-sufficient patients were analyzed. RESULTS: Meningitis without meningococcemia accounted for 17% of the MD episodes in the control group of complement-sufficient patients but none in individuals with TCCD who had meningococcemia (10%) or meningococcemia with meningitis (90%). Moderate disease predominated in patients with TCCD (70%) and no episodes of fatal disease were noted, whereas severe disease was more common in the control group which had an 8% case fatality rate and frequent complications such as endotoxic shock (15% of episodes) and brain edema (26%). The severity of the disease in TCCD patients did not differ between the first and subsequent episodes, between males and females, between episodes caused by serogroup A and B meningococci, etc. CONCLUSION: In comparison to complement-sufficient persons, the course of the disease in patients with TCCD is statistically less severe.

Adolescent↗
PubMed2001

Cytosolic phospholipase A2-alpha associates with plasma membrane, endoplasmic reticulum and nuclear membrane in glomerular epithelial cells.

Eicosanoids mediate complement-dependent glomerular epithelial injury in experimental membranous nephropathy. The release of arachidonic acid from phospholipids by cytosolic phospholipase A(2) (cPLA(2)) is the rate-limiting step in eicosanoid synthesis. The present study examines the association of cPLA(2) with membranes of organelles. Glomerular epithelial cells were disrupted by homogenization in Ca(2+)-free buffer; organelles were separated by gradient centrifugation. The distribution of cPLA(2) and organelles was analysed by immunoblotting with antibodies against cPLA(2) and organelle markers, or by enzyme assay. In cells incubated with or without the Ca(2+) ionophore ionomycin plus PMA, cPLA(2) co-localized with plasma membrane, endoplasmic reticulum and nuclei, but not with mitochondria or Golgi. A greater amount of cPLA(2) was associated with membranes in stimulated cells, but membrane-associated cPLA(2) was readily detectable under resting conditions. The pattern of association of cPLA(2) with membrane in cells treated with antibody and complement was similar to that in cells stimulated with ionomycin plus PMA; however, complement did not enhance the membrane association of cPLA(2) protein. To determine the functional role of membrane association of cPLA(2), phospholipids were labelled with [(3)H]arachidonic acid. Cells were then incubated with or without antibody and complement and were fractionated. Complement induced a loss of radioactivity from the plasma membrane, endoplasmic reticulum and nuclei, but not from the mitochondrial fraction. Thus the release of arachidonic acid by cPLA(2) is due to the hydrolysis of phospholipids at multiple subcellular membrane sites, including the endoplasmic reticulum, plasma membrane and nucleus.

Animals↗
PubMedDate not supplied

Pathogenetic concepts of membranous glomerulopathy (MGN).

Membranous glomerulopathy (MGN) is a frequent cause for nephrotic syndrome in adults. In this overview, the basic pathogenic features of Heymann nephritis, a "classical" model of MGN in rats, are compared with those of human MGN. While the pathogenic antigen(s) of rat Heymann nephritis (the polyspecific receptor protein gp330/megalin), and that of human MGN (unknown) are obvioulsy different, the results indicate that the molecular mechanisms of proteinuria may be similar in both instances and involve the formation of lipid peroxidation adducts in the glomerular capillary filter. As a consequence, probucol - an efficient inhibitor of lipid peroxidation - drastically reduces proteinuria both in Heymann nephritis and in a large proportion of human patients with MGN.

Basement Membrane↗
PubMed2000

[C6 deficiency].

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Autoimmune Diseases↗
PubMed2000

[C7 deficiency].

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Autoimmune Diseases↗
PubMed1992

Evaluation of endometrial tissue specific complement activation in women with endometriosis.

OBJECTIVE: To determine if endometrial tissue specific complement (C) activation occurs in patients with endometriosis. DESIGN: Prospective. SETTING: University of Oklahoma Health Sciences Center, a tertiary care referral center. PATIENTS: Twenty-six women, 9 with endometriosis and 17 without endometriosis. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Uterine and ectopic endometria were evaluated by the immunofluorescence assay for the presence of activated products of the initial (C3d) and terminal (C5b-9) C pathway, C3 regulatory proteins (decay-accelerating factor and membrane cofactor protein), and terminal C regulatory proteins (clusterin and vitronectin). RESULTS: The initial (C3d) and terminal (C5b-9) C components were deposited on blood vessel walls in uterine and/or ectopic endometria of women with and without endometriosis. In the stromal compartment at both sites, C deposition was colocalized with terminal C inhibitors/cell-cell attachment factors, clusterin and vitronectin on elastic fibers. No specific staining for C proteins was detected on the glandular epithelium of uterine and ectopic endometrial tissues examined. Furthermore, intense staining of endometrial epithelium for C3 regulatory proteins, decay-accelerating factor, and membrane cofactor protein was noted on endometrial glands from women with and without endometriosis. CONCLUSIONS: Our findings demonstrate a lack of specific deposition of C in the glandular epithelial cells of endometria of women with endometriosis. The localization of C3 regulatory proteins, decay-accelerating factor, and membrane cofactor protein on glandular epithelium may suggest the involvement of intrinsic protective mechanisms on these cells from autologous C attack in vivo.

Adult↗
PubMed2003

[Interleukin-18 and its related cytokines in plasma of patients with idiopathic thrombocytopenic purpura].

To explore the role of immune regulating cytokines in pathogenesis of the idiopathic thrombocytopenic purpura (ITP) and its clinical significance, the levels of IL-18, TNF-alpha and Sc5b-9 in plasma of 32 ITP patients and 18 normal individuals were detected using ELISA methods. The results showed that IL-18, TNF-alpha and sC5b-9 levels in plasma of ITP patients were higher than that in normal individuals. The level of IL-18 was positively correlated with the levels of TNF-alpha and sC5b-9. In conclusion, The rising levels of the IL-18, TNF-alpha and sC5b-9 were correlated with disorder of Th1/Th2 subsets, and may contribute to the immune dysfunction in ITP patients. The dynamic observation of these cytokines may be useful in directing the clinical treatment for ITP patients.

Adolescent↗
PubMed2004

Docetaxel (taxotere) induced subacute cutaneous lupus erythematosus: report of 4 cases.

OBJECTIVE: We describe 4 patients who developed subacute cutaneous lupus erythematosus (SCLE)-like photodistributed eruptions after ingestion of docetaxel (Taxotere). The development of SCLE-like cutaneous eruptions has been associated with the intake of drugs including thiazide diuretics, calcium channel blockers, angiotensin converting-enzyme inhibitors, phenytoin, etanercept, antihistaminics, interferons, statins, and terbinafine. Docetaxel, a chemotherapeutic drug used in breast cancer therapy, has not to our knowledge been reported to cause SCLE. METHODS: Skin biopsies were obtained from 4 patients with photodistributed rashes while taking docetaxel. RESULTS: In all patients, skin biopsies were remarkable for an atrophying interface dermatitis associated with mucin deposition. Immunofluorescent testing revealed the characteristic pattern of SCLE, namely, granular epidermal keratinocyte deposition of IgG and C5b-9. The eruptions resolved following cessation of the drug. CONCLUSION: Pathogenetically, docetaxel may evoke a lupus-like eruption through its proapoptotic effects on replicating cells, which could in turn provoke the release of nucleosomes postulated to be target antigens in LE. It seems reasonable to postulate that the rapidly replicating keratinocyte, when subjected to the cytotoxic effects of docetaxel, would also manifest nucleosome release followed by a local autoimmune reaction in a genetically predisposed host.

Aged↗
PubMed2004

[Inhibitory effect of hDAF displayed on yeast cells on deposition of complement on the yeast cells].

AIM: To investigate whether the hDAF displayed on the surface of yeast cells can inhibit the deposition of C5b-9. METHODS: After treatment with normal human serum, deposition of human complement C5b-9 and DAF expression on yeast cells EBY100 were analyzed by flow cytometry. RESULTS: Yeast cells EBY100 could activate the complement molecules in human serum and lead to the deposition of C5b-9, while the deposition of C5b-9 on the surface of yeast cells with hDAF could significantly reduce the deposition of C5b-9. CONCLUSION: hDAF displayed on the surface of yeast cells can fold correctly and exhibit activity of complement's inhibition.

CD55 Antigens↗