Complement induces a transient increase in membrane permeability in unlysed erythrocytes.

Halperin, José A.; Nicholson‐Weller, Anne; Brugnara, Carlo; Tosteson, D. C.

doi:10.1172/jci113637

Cited by 34 publications

(15 citation statements)

References 35 publications

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“…On the basis of the present and previous results, we hypothesize that diabetesinduced alternations in enzymatic glycosylations and/or increased formation of advanced glycation end products lead to formation of patterns recognized by MBL. As shown in vitro, complement activation and sublytic formation of the terminal complement complex on mammalian cells may induce release of growth factors, leading to vascular alternations (26)(27)(28)(29)(30)(31). In addition, glycation of complement regulatory proteins has been shown to decrease their regulatory capacity and increase complement activation in diabetes (32,33).…”

Section: Discussionmentioning

confidence: 99%

Increased All-Cause Mortality in Patients With Type 1 Diabetes and High-Expression Mannan-Binding Lectin Genotypes: A 12-Year Follow-up Study

et al. 2015

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OBJECTIVEMannan-binding lectin (MBL) is a complement-activating carbohydrate-recognizing molecule associated with diabetic nephropathy. MBL is associated with all-cause mortality in type 2 diabetes, but whether MBL is associated with mortality in type 1 diabetes remains unknown. We therefore aimed to investigate this. RESEARCH DESIGN AND METHODSWe studied an existing 12-year prospective cohort with RESULTSNinety-eight patients died during follow-up. The unadjusted hazard ratio (HR) for all-cause mortality was 1.61 (95% CI 1.07-2.43) for patients with high MBL expression genotypes versus patients with low MBL expression genotypes (P = 0.023). All-cause mortality was higher in patients with MBL concentrations above the median than in patients with MBL concentrations below the median (unadjusted HR 1.90 [95% CI 1.26-2.87], P = 0.002). CONCLUSIONSHigh MBL expression genotypes and high MBL concentrations are both associated with increased mortality rates in type 1 diabetes compared with low MBL expression genotypes and low MBL concentrations.Late diabetes complications contribute to excess morbidity and mortality in diabetes. The complement cascade of the immune system is most likely implicated in the development of these complications (1). Diabetes may induce the formation of complement-activating ligands by two mechanisms: altered enzymatic protein glycosylation and increased nonenzymatic advanced glycation end product formation. Both products are hypothesized to be adversely recognized by complement-activating

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Section: Discussionmentioning

confidence: 99%

Increased All-Cause Mortality in Patients With Type 1 Diabetes and High-Expression Mannan-Binding Lectin Genotypes: A 12-Year Follow-up Study

et al. 2015

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“…Experiments with cells separated by density using Stractan (23). Presumably, Ca2+ also diffuses through the transient complement lesion, which is known to allow for the entry of both Na+ and glucose into the cell (4). Indirect evidence for a role of the Ca2+-induced K+ transport pathway was provided using carbocyanine, a specific inhibitor of this K+ transport pathway.…”

Section: Discussionmentioning

confidence: 99%

“…However, we have recently reported that under conditions of limited complement activation the MAC may cause a large but transient increase in cell membrane permeability, and the affected cells do not lyse (4). In addition, we also observed that the cells surviving sublytic complement attack do not swell even though they experience a substantial increase in the permeability of their membranes, documented by a marked reduction in intracellular K+ (Kt) and an increase in intracellular Na' (Naj).…”

Section: Introductionmentioning

confidence: 88%

Ca2+-activated K+ efflux limits complement-mediated lysis of human erythrocytes.

Halperin¹,

Brugnara²,

Nicholson‐Weller³

1989

J. Clin. Invest.

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The lytic effect of complement on human erythrocytes has been reported by others to increase when Na+ is substituted for K+ in the external medium. In this paper we have investigated the hypothesis that net loss of K+ through a K+ transport pathway protects erythrocytes from complement-induced colloidosmotic swelling and lysis. Antibody-sensitized human erythrocytes containing different intracellular cation concentrations (nystatin treatment) were exposed to low concentrations of guinea pig serum in media of different cation composition; complement lysis was assessed by the release of hemoglobin and the volume of the surviving cells estimated by their density distribution profiles. Complement-dependent swelling and lysis of erythrocytes (a) were limited by the presence of an outwardly directed K+ electrochemical gradient and (b) were enhanced by carbocyanine, a specific inhibitor of the Ca2'-activated K+ transport pathway, and by absence of Ca2`in the external medium. We propose that during complement activation a rising cytosolic calcium triggers the Ca2+-activated K+ permeability pathway, the Gardos effect, produces a net K+, Cl-and water loss, and thus limits the colloidosmotic swelling and lysis of erythrocytes.

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“…A number of investigators have attempted to isolate and identify an endogenous counterpart to the cardiac glycosides from a variety of sources, such as plasma [30 -32, 461, urine [9,10,30], cerebrospinal fluid [47], hypothalamus [I 3,151 and adrenal gland [35]. Although several compounds have been isolated and identified as endogenous substances with the inhibitor activity, most of them have been shown to be nonspecific, low-affinity inhibitors for Na+,K+-ATPase.…”

Section: Discussionmentioning

confidence: 99%

Isolation and characterization of an endogenous Na⁺,K⁺ ‐ATPase‐specific inhibitor from pig urine

Tamura

Harris

Konishi

et al. 1993

European Journal of Biochemistry

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A Na+,K+-ATPase inhibitor was purified from 88.6 1 pig urine with a yield of approximately 10 pg. It inhibits the ouabain-sensitive uptake of "Rb into human erythrocytes and the specific binding of ouabain to Na+,K+-ATPase. It also exhibits cross-reactivity to anti-ouabain serum. The purification procedure consisted of adsorption chromatography on an Amberlite XAD-2 column, preparative scale CI8 low-pressure liquid chromatography (LPLC), and five steps of HPLC with five different types of reverse-phase columns. The dose dependence of the purified substance for the inhibition of ouabain-sensitive Na+,K ' -ATPase activity and 86Rb uptake into human erythrocytes, and for the ouabain-displacing activity, paralleled those of ouabain, spanning two orders of magnitude in concentration range. However, the curve obtained from the cross-immunoreactivity with antiouabain serum did not parallel that of ouabain. The inhibitory potencies of the purified substance against the Na+-pump and ouabain-binding were diminished with increasing K' concentration, exhibiting characteristics typical of cardiac glycosides. This substance had no effect on Ca2 +-ATPase activity in human erythrocyte plasma membrane and skeletal-muscle sarcoplasmic reticulum, nor on Mg2+-ATPase activity. Acid treatment with 6 M HC1 at 115°C for less than 1 min destroyed approximately 82% of the inhibitory activity of the purified substance against Na+-pump activity. Alkaline treatment with 0.2 M NaOH at 23°C for 2 h and heat treatment at 150°C for 30 min

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Complement induces a transient increase in membrane permeability in unlysed erythrocytes.

Cited by 34 publications

References 35 publications

Increased All-Cause Mortality in Patients With Type 1 Diabetes and High-Expression Mannan-Binding Lectin Genotypes: A 12-Year Follow-up Study

Increased All-Cause Mortality in Patients With Type 1 Diabetes and High-Expression Mannan-Binding Lectin Genotypes: A 12-Year Follow-up Study

Ca2+-activated K+ efflux limits complement-mediated lysis of human erythrocytes.

Isolation and characterization of an endogenous Na⁺,K⁺ ‐ATPase‐specific inhibitor from pig urine

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Complement induces a transient increase in membrane permeability in unlysed erythrocytes.

Cited by 34 publications

References 35 publications

Increased All-Cause Mortality in Patients With Type 1 Diabetes and High-Expression Mannan-Binding Lectin Genotypes: A 12-Year Follow-up Study

Increased All-Cause Mortality in Patients With Type 1 Diabetes and High-Expression Mannan-Binding Lectin Genotypes: A 12-Year Follow-up Study

Ca2+-activated K+ efflux limits complement-mediated lysis of human erythrocytes.

Isolation and characterization of an endogenous Na+,K+ ‐ATPase‐specific inhibitor from pig urine

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Isolation and characterization of an endogenous Na⁺,K⁺ ‐ATPase‐specific inhibitor from pig urine