Activated complement directly modifies the performance of isolated heart muscle cells from guinea pig and rat

Berger, Hans; Taratuska, A; Smith, Thomas W.; Halperin, José A.

doi:10.1152/ajpheart.1993.265.1.h267

Cited by 17 publications

(9 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…and contractility (Berger et al, 1993). Thus, it seems plausible that the deposition of MACs on the membranes of a small subset of hippocampal neurons may trigger similar cation fluxes and depolarization; the resulting high-frequency firing of this subset might recruit otherwise unaffected but synaptically coupled neurons into a larger neuronal population firing synchronously, thus mediating the electrographic and behavioral seizures observed in this study.…”

Section: Discussionmentioning

confidence: 72%

Formation of Complement Membrane Attack Complex in Mammalian Cerebral Cortex Evokes Seizures and Neurodegeneration

et al. 2003

View full text Add to dashboard Cite

The complement system consists of Ͼ30 proteins that interact in a carefully regulated manner to destroy invading bacteria and prevent the deposition of immune complexes in normal tissue. This complex system can be activated by diverse mechanisms proceeding through distinct pathways, yet all converge on a final common pathway in which five proteins assemble into a multimolecular complex, the membrane attack complex (MAC). The MAC inserts into cell membranes to form a functional pore, resulting in ion flux and ultimately osmotic lysis. Immunohistochemical evidence of the MAC decorating neurons in cortical gray matter has been identified in multiple CNS diseases, yet the deleterious consequences, if any, of MAC deposition in the cortex of mammalian brain in vivo are unknown. Here we demonstrate that the sequential infusion of individual proteins of the membrane attack pathway (C5b6, C7, C8, and C9) into the hippocampus of awake, freely moving rats induced both behavioral and electrographic seizures as well as cytotoxicity. The onset of seizures occurred during or shortly after the infusion of C8/C9. Neither seizures nor cytotoxicity resulted from the simultaneous infusion of all five proteins premixed in vitro. The requirement for the sequential infusion of all five proteins together with the temporal relationship of seizure onset to infusions of C8/C9 implies that the MAC was formed in vivo and triggered both seizures and cytotoxicity. Deposition of the complement MAC in cortical gray matter may contribute to epileptic seizures and cell death in diverse diseases of the human brain.

show abstract

Section: Discussionmentioning

confidence: 72%

Formation of Complement Membrane Attack Complex in Mammalian Cerebral Cortex Evokes Seizures and Neurodegeneration

et al. 2003

View full text Add to dashboard Cite

show abstract

“…The formation of the MAC pore, however, seems to be the end stage of a process that transits through a reversible phase during which MAC pores can be formed transiently (32)(33)(34), generating significant changes in the membrane permeability and internal composition of MAC-targeted cells without compromising their viability (32,35,36). Figure 2 illustrates the large increase of intracellular Ca ϩϩ levels caused by transient, nonlytic MAC pores on isolated guinea-pig cardiomyocytes (36). Thus, whereas the matured MAC pore can kill nonself cells by perforating their plasma membrane, the transient MAC pore can induce nonlethal biological responses in "self" cells and mediate physiological and/or pathological response (37).…”

Section: The Mac: Formation and Functionmentioning

confidence: 99%

“…49), including increased: 1) Ca ϩϩ influx (36,50) and Ca ϩϩ -activated K ϩ efflux (35); 2) production of ROS (51,52); 3) activation of Ca ϩϩ -sensitive and Ca ϩϩ -insensitive PKC (53, 54); 4) activation of heterotrimeric G proteins of the Gi/Go subfamily (55); 5) mitotic signaling through the small G protein Ras, which induces Raf-1 translocation triggering activation of the ERK pathway (56); and 6) activation of phosphatidylinositol-3 kinase (57). The MAC also activates the transcription factor nuclear factor-B (NF-B), which induces the production of IL-6 as well as IL-8 and MCP-1 (58,59).…”

Section: The Mac As a Mediator Of Cellular Signaling And An Effementioning

confidence: 99%

Role of Complement and Complement Regulatory Proteins in the Complications of Diabetes

et al. 2015

View full text Add to dashboard Cite

It is well established that the organ damage that complicates human diabetes is caused by prolonged hyperglycemia, but the cellular and molecular mechanisms by which high levels of glucose cause tissue damage in humans are still not fully understood. The prevalent hypothesis explaining the mechanisms that may underlie the pathogenesis of diabetes complications includes overproduction of reactive oxygen species, increased flux through the polyol pathway, overactivity of the hexosamine pathway causing intracellular formation of advanced glycation end products, and activation of protein kinase C isoforms. In addition, experimental and clinical evidence reported in past decades supports a strong link between the complement system, complement regulatory proteins, and the pathogenesis of diabetes complications. In this article, we summarize the body of evidence that supports a role for the complement system and complement regulatory proteins in the pathogenesis of diabetic vascular complications, with specific emphasis on the role of the membrane attack complex (MAC) and of CD59, an extracellular cell membrane-anchored inhibitor of MAC formation that is inactivated by nonenzymatic glycation. We discuss a pathogenic model of human diabetic complications in which a combination of CD59 inactivation by glycation and hyperglycemia-induced complement activation increases MAC deposition, activates pathways of intracellular signaling, and induces the release of proinflammatory, prothrombotic cytokines and growth factors. Combined, complement-dependent and complement-independent mechanisms induced by high glucose promote inflammation, proliferation, and thrombosis as characteristically seen in the target organs of diabetes complications.

show abstract

“…Furthermore, myocardial ischemia itself, regardless of CPB, can result in activation of complement such as C5b9. 41 Hence, both techniques can activate the inflammatory response during periods of myocardial ischemia. Furthermore, in many of these trials, cardiotomy suction and non-heparin-bonded circuits were used in the on-pump CABG patients; these factors are known to increase complement activation and contribute to the inflammatory response.…”

Section: Inflammatory Responses and Biomarkersmentioning

confidence: 99%

Should Off-Pump Coronary Artery Bypass Grafting Be Abandoned?

Lazar

2013

Circulation

View full text Add to dashboard Cite

406O ne of the most controversial areas of cardiac surgery has been whether off-pump coronary artery bypass graft (OPCAB) surgery is superior to traditional on-pump coronary artery bypass graft (CABG) surgery. On-pump CABG surgery has been an effective, safe, and time-proven technique and is the gold standard with which all other surgical revascularization methods have been compared. However, performing coronary revascularization on cardiopulmonary bypass (CPB) can result in myocardial ischemic injury, neurocognitive deficits, and strokes and activate inflammatory pathways that contribute to pulmonary, renal, and hematologic complications. OPCAB offered a promising alternative strategy that had the potential to decrease perioperative morbidity, mortality, and cost by eliminating CPB. In fact, throughout Asia and particularly in India, 95% of CABG surgery is performed offpump. In North America, OPCAB procedures peaked at 25% in 2004 and have declined steadily since that time.1 It is a more technically demanding procedure and results in less complete revascularization. There is growing concern that OPCAB is associated with reduced long-term graft patency and increased need for revascularization procedures and results in inferior long-term survival compared with traditional on-pump CABG surgery.In view of these concerns, should OPCAB be abandoned? The purpose of this review is to examine clinical data that most accurately compare the advantages and disadvantages of OPCAB to determine what, if any, role it should have in the practice of surgical coronary artery revascularization. To reach these conclusions, retrospective nonrandomized, prospective randomized, and meta-analyses trials will be reviewed. The effect of incomplete revascularization and conversion to conventional CABG will be examined. The relationship between OPCAB and the inflammatory response, neurological and cognitive changes, and quality of life will be studied, and the impact of OPCAB on sex, renal transplant recipients, and elderly patients will be determined. Retrospective StudiesRetrospective studies were largely single center and lacked randomization. Surgeons who were more skilled in OPCAB were more likely to perform these procedures. Hence, there was a significant selection bias. In most studies, the intentionto-treat principle was not honored. Therefore, if a patient was converted to an on-pump CABG, an adverse outcome associated with this patient would be attributed to the on-pump CABG and not the originally planned OPCAB. Earlier studies may have lacked proper stabilizing equipment and intracoronary perfusion devices. Many trials reported only short-term outcomes. The retrospective studies discussed in this section generally involve >1 surgeon, had larger sample sizes to detect statistically significant differences in clinical outcomes, and contained long-term data.One of the largest databases used to compare outcomes between OPCAB and on-pump CABG techniques involved the New York State Registry for CABG Surgery. Racz and coworkers 2 first...

show abstract

Activated complement directly modifies the performance of isolated heart muscle cells from guinea pig and rat

Cited by 17 publications

References 0 publications

Formation of Complement Membrane Attack Complex in Mammalian Cerebral Cortex Evokes Seizures and Neurodegeneration

Formation of Complement Membrane Attack Complex in Mammalian Cerebral Cortex Evokes Seizures and Neurodegeneration

Role of Complement and Complement Regulatory Proteins in the Complications of Diabetes

Should Off-Pump Coronary Artery Bypass Grafting Be Abandoned?

Contact Info

Product

Resources

About