Evidence for iC3 generation during cardiopulmonary bypass as the result of blood-gas interaction

Pekna, Marcela; Nilsson, Leif; Nilsson‐Ekdahl, Kristina; Nilsson, Ulf; Nilsson, Bo

doi:10.1111/j.1365-2249.1993.tb05916.x

Cited by 46 publications

(23 citation statements)

References 29 publications

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“…factor H). It has previously been demonstrated that by this definition, C3(H 2 O) occurs on polystyrene surfaces [52], on human platelets [53], and at blood-gas [54] and plasmae–gas interfaces [8]. The polystyrene surface and the platelet membrane are solid surfaces when compared to the variable surfaces formed by gas bubbles.…”

Section: Discussionmentioning

confidence: 99%

Mediation of a non-proteolytic activation of complement component C3 by phospholipid vesicles

et al. 2014

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Liposomes are becoming increasingly important as drug delivery systems, to target a drug to specific cells and tissues and thereby protecting the recipient from toxic effects of the contained drug. Liposome preparations have been described to activate complement. In this study, we have investigated complement activation triggered by neutral dimyristoyl-phosphocholine (DMPC) liposomes in human plasma and whole-blood systems. Incubation in plasma led to the generation of complement activation products (C3a and sC5b-9). Unexpectedly, investigations of surface-bound C3 revealed contact activated, conformationally changed C3 molecules on the liposomes. These changes were characterized by Western blotting with C3 monoclonal antibodies, and by incubating liposomes with purified native C3 and factors I and H. Quartz crystal microbalance analysis confirmed binding of C3 to planar DMPC surfaces. In addition, we demonstrated that DMPC liposomes bound to or were phagocytized by granulocytes in a complement-dependent manner, as evidenced by the use of complement inhibitors. In summary, we have shown that C3 is activated both by convertase-dependent cleavage, preferentially in the fluid phase, by mechanisms which are not well elucidated, and also by contact activation into C3(H2O) on the DMPC surface. In particular, this contact activation has implications for the therapeutic regulation of complement activation during liposome treatment.

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Section: Discussionmentioning

confidence: 99%

Mediation of a non-proteolytic activation of complement component C3 by phospholipid vesicles

et al. 2014

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“…Complement factor C3, a downstream factor of MASP-2, was reported to be activated in peripheral circulation in patients undergoing open heart surgery with CPB [30, 31], and was associated with pathogenic post-operation conditions [32–36]. It has been reported that post-operative peak cTnI >13ng/ml was an independent predictor of short and mid-term clinical outcome after cardiac surgery [37].…”

Section: Discussionmentioning

confidence: 99%

MASP-2 activation is involved in ischemia-related necrotic myocardial injury in humans

Zhang

Hou

Çavuşoğlu

et al. 2013

International Journal of Cardiology

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Background/Objectives Insufficient blood supply to the heart results in ischemic injury manifested clinically as myocardial infarction (MI). Following ischemia, inflammation is provoked and related to the clinical outcomes. A recent basic science study indicates that complement factor MASP-2 plays an important role in animal models of ischemia/reperfusion injury. We investigated the role of MASP-2 in human acute myocardial ischemia in two clinical settings: (1) Acute MI, and (2) Open heart surgery. Methods A total of 187 human subjects were enrolled in this study, including 50 healthy individuals, 27 patients who were diagnosed of coronary artery disease (CAD) but without acute MI, 29 patients with acute MI referred for coronary angiography, and 81 cardiac surgery patients with surgically-induced global heart ischemia. Circulating MASP-2 levels were measured by ELISA. Results MASP-2 levels in the peripheral circulation were significantly reduced in MI patients compared with those of healthy individuals or of CAD patients without acute MI. The hypothesis that MASP-2 was activated during acute myocardial ischemia was evaluated in cardiac patients undergoing surgically-induced global heart ischemia. MASP-2 was found to be significantly reduced in the coronary circulation of such patients, and the reduction of MASP-2 levels correlated independently with the increase of the myocardial necrosis marker, cardiac troponin I. Conclusions These results indicate an involvement of MASP-2 in ischemia-related necrotic myocardial injury in humans.

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“…This form of C3 has C3b-like properties, in that it is capable of binding factor B and factor H and of forming a fluid-phase AP convertase (Pangburn and Müller-Eberhard, 1983;Pangburn et al, 1981). We have previously demonstrated the generation of C3(H 2 O) in vitro when gas is bubbled through whole blood (Ekdahl et al, 1992), and in vivo during CPB to a maximal level of 100 nM, which corresponds to hydrolysis of approximately 1% of the total pool of C3 (Pekna et al, 1993). This result indicates that the molecular ratio between C3(H 2 O) and factor B in vivo would be 1:20 (0.1:2 μM), and it is thus reasonable to postulate that the equilibrium in that situation would favor the formation of C3(H 2 O)/Bb convertase in the fluid phase.…”

Section: Discussionmentioning

confidence: 99%

“…This reaction constantly takes place at a low rate (tickover) in blood (Pangburn and Müller-Eberhard, 1983;Pangburn et al, 1981). We have demonstrated the generation of C3(H 2 O) at the interface between blood and gas in an in vitro model of cardiopulmonaty bypass (CPB) and in vivo in patients during CPB (Ekdahl et al, 1992;Pekna et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

The tick-over theory revisited: Formation and regulation of the soluble alternative complement C3 convertase (C3(H2O)Bb)

Bexborn¹,

Andersson

Chen

et al. 2008

Molecular Immunology

134

124

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The molecular interactions between the components of the C3 convertase of the alternative pathway (AP) of complement and its regulators, in both surface-bound and fluid-phase form, are still incompletely understood. The fact that the AP convertase is labile makes studies difficult to perform. According to the so called tick-over theory, hydrolyzed C3, called C3(H(2)O), forms the initial convertase in fluid phase together with factor B. In the present study, we have applied western blot analysis and ELISA together with fluorescence resonance energy transfer (FRET) to study the formation of the fluid-phase AP convertases C3(H(2)O)Bb and C3bBb and their regulation by factor H and factor I at specific time points and, with FRET, in real time. In our hands, factor B showed a higher affinity for C3(H(2)O) than for C3b, although in both cases it was readily activated to Bb. However, the convertase activity of C3bBb was approximately twice that of C3(H(2)O)Bb, as monitored by the generation of C3a. But in contrast, the C3(H(2)O)Bb convertase was more resistant to inactivation by factor H and factor I than was the C3bBb convertase. Under conditions that totally inactivated C3bBb, C3(H(2)O)Bb still retained approximately 25% of its initial activity.

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Evidence for iC3 generation during cardiopulmonary bypass as the result of blood-gas interaction

Cited by 46 publications

References 29 publications

Mediation of a non-proteolytic activation of complement component C3 by phospholipid vesicles

Mediation of a non-proteolytic activation of complement component C3 by phospholipid vesicles

MASP-2 activation is involved in ischemia-related necrotic myocardial injury in humans

The tick-over theory revisited: Formation and regulation of the soluble alternative complement C3 convertase (C3(H2O)Bb)

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