The consequences of complement activation and the symptoms of decompression sickness are similar. Consequently, the relation between the sensitivity of individuals to complement activation by air bubbles and their susceptibility to decompression sickness has been examined. Plasma samples from 34 individuals were incubated with air bubbles, and the concentration of the fluid phase metabolites of complement activation C3a, C4a, and C5a were measured with radioimmunoassays. It was found that both the anaphylatoxins C3a and C5a were produced by the presence of air bubbles but that the anaphylatoxin C4a was not. This finding indicates that air bubbles activate the complement system by the alternate pathway. One group of individuals was found to be particularly sensitive to complement activation by this pathway. They produced 3.3 times more C3a and 5.3 times more C5a in their plasma samples incubated with air bubbles as did the other group. Sixteen individuals were subjected to a series of pressure profiles that were severe enough to produce bubbles in their circulatory system that could be detected by Doppler ultrasonic monitoring. The group of individuals that had been identified as being more sensitive to complement activation by the alternate pathway was also found to be more susceptible to decompression sickness.
The possibility of the air-plasma interface giving rise to complement activation is investigated. After incubation of the plasma of a group of rabbits with zymosan and measurement of the degree of autologous polymorphonuclear leukocyte aggregation that follows the injection of a sample of the incubated plasma into a leukocyte suspension, it is found that the rabbits can be divided into two groups, sensitive and insensitive, depending on the degree of leukocytes aggregation. For the sensitive group it is found that both the plasma-air interface and the serum-air interface give rise to significant leukocyte aggregation. If the animal is decomplemented before the plasma is incubated in the presence of the air interface, there is no longer any significant leukocyte aggregation. It would appear that the complement system is activated by the presence of the air interface in plasma, but that fibrinogen does not play a pivotal role in the process.
Biomaterials activate the complement system which is important since C3a promotes platelet aggregation and release, and C5a activates neutrophils that may augment coagulation. Tiny air nuclei (microbubbles) are found in the surface roughness of biomaterials on exposure to a liquid, therefore two interfaces exist: (a) a blood/biomaterial, and (b) a blood/air interface. Experiments were carried out that documented that air bubbles activate complement and augment in vitro platelet aggregation in human plasma. The air nuclei were removed from the surface of silicone rubber by a technique termed denucleation to determine if complement activation and platelet aggregation could be reduced. We observed a significant reduction in C3a and C5a in the plasma samples incubated with denucleated silicone rubber as compared to the control samples (p less than 0.001, ANOVA). The plasma incubated with the denucleated silicone caused reduced platelet aggregation as compared to the plasma incubated with the control silicone when added to a platelet suspension (p less than 0.001, ANOVA). Surface chemical analysis by x-ray photo-electron spectroscopy (XPS) showed no change in the silicone rubber surface after the denucleation procedure.
Complement activation by biomaterials may play an important role in vascular graft failure since the physiologically active polypeptides, C3a and C5a, have several relevant properties. C3a promotes platelet aggregation and release, and C5a activates neutrophils, which may stimulate platelet aggregation by liberation of platelet activating factor or by a direct neutrophil platelet interaction. Microscopic air bubbles (nuclei) are found in the surface roughness or pores of most biomaterials, and their number and size are related to the surface tension of the material. Therefore two interfaces can be postulated to exist when Dacron is exposed to blood: (1) a blood/biomaterial, and (2) a blood/air interface. These air nuclei in the surface and the biomaterial itself are capable of activating complement. The purpose of these experiments was to eliminate these surface nuclei from Dacron by a process termed denucleation and subsequently to determine the effect of this intervention on complement activation and platelet aggregation in vitro. Dacron was denucleated by pretreatment that involved serial rinsing with ethanol and degassed buffer that results in replacement of the air nuclei by buffer. Both control and denucleated pieces of Dacron (2, 4, and 6 cm2) were then incubated in human plasma. Each plasma sample was assayed for complement activation products (C3a, C5a, and C4a) by means of radioimmunoassays, and the degree of autologous platelet aggregation that resulted from the addition of a portion of each incubated plasma sample to an autologous platelet suspension was measured. There was a significant reduction in C3a and C5a in the plasma samples incubated with denucleated Dacron as compared to control Dacron (p less than 0.001, analysis of variance [ANOVA]).(ABSTRACT TRUNCATED AT 250 WORDS)
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.