REQUIREMENT FOR C5a IN LUNG VASCULAR INJURY FOLLOWING THERMAL TRAUMA TO RAT SKIN

Schmid, Elisabeth; Piccolo, M.T.S.; Friedl, H. P.; Warner, Roscoe L.; Mulligan, Michael S.; Hugli, Tony E.; Till, Gerd O.; Ward, Peter A.

doi:10.1097/00024382-199708000-00010

Cited by 30 publications

(17 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To date, the potential role of complement activation products in the setting of cardiac dysfunction following burn injury has not been investigated. It is well known that burn injuries lead to extensive activation of the complement system, producing C5a and other products (11,25). Recently, we demonstrated the expression of the C5a receptor, C5aR, on isolated rat CMs.…”

Section: Discussionmentioning

confidence: 88%

C5a-Blockade Improves Burn-Induced Cardiac Dysfunction

Hoesel

Niederbichler²,

Schaefer

et al. 2007

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

We previously reported that generation of the anaphylatoxin C5a is linked to the development of cardiac dysfunction in sepsis due to C5a interaction with its receptor (C5aR) on cardiomyocytes. Burn injury involves inflammatory mechanisms that can lead to C5a generation as well. In this study, we investigated the effects of C5a blockade on burn-induced cardiac dysfunction. Using a standardized rat model of full thickness scald injury, left ventricular pressures were recorded in vivo followed by in vitro assessment of sarcomere contraction of single cardiomyocytes. Left ventricular pressures in vivo and cardiomyocyte sarcomere contractility in vitro were significantly reduced following burn injury. In the presence of anti-C5a Ab, these defects were greatly attenuated 1, 6, and 12 h after burn injury and completely abolished 24 h after burn. In vitro incubation of cardiomyocytes with bacterial LPS accentuated the impaired contractility, which was partially prevented in cardiomyocytes from burned rats that had received an anti-C5a Ab. Based on Western blot analyses, real-time PCR, and immunostaining of left ventricular heart tissue, there was a significant increase in cardiomyocyte expression of C5aR after burn injury. In conclusion, an in vivo blockade of C5a attenuates burn-induced cardiac dysfunction. Further deterioration of contractility due to the exposure of cardiomyocytes to LPS was partially prevented by C5a-blockade. These results suggest a linkage between C5a and burn-induced cardiac dysfunction and a possible contribution of LPS to these events.

show abstract

Section: Discussionmentioning

confidence: 88%

C5a-Blockade Improves Burn-Induced Cardiac Dysfunction

Hoesel

Niederbichler²,

Schaefer

et al. 2007

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

show abstract

“…anaphylotoxin C5a have been detected in serum and lung homogenates after thermal injury (22). Treatment of animals with a polyclonal neutralizing antibody to C5a before burn injury resulted in diminished vascular permeability changes and reduced tissue buildup of myeloperoxidase within the lung.…”

Section: Discussionmentioning

confidence: 99%

Cardiomyocyte Function After Burn Injury and Lipopolysaccharide Exposure: Single-Cell Contraction Analysis and Cytokine Secretion Profile

Niederbichler¹,

Westfall²,

et al. 2006

Shock

View full text Add to dashboard Cite

A component of multiorgan dysfunction in burned patients is heart failure. Burn trauma induces cytokine synthesis of interleukin (IL) 1beta, IL-6, and tumor necrosis factor alpha (TNF-alpha) which can negatively impact cardiac function. Infectious complications are common following severe burn injury. We hypothesized that burn injury and lipopolysaccharide (LPS) exposure independently influence peak cardiomyocyte contraction and cytokine secretion. Rats underwent a full-thickness 30% total body surface area scald or sham burn. At 1, 6, 12, and 24 h after burn, cardiomyocytes were isolated and incubated with increasing LPS doses. Peak sarcomere shortening and contractile velocity parameters were recorded using a variable-rate video camera with sarcomere length detection software. Supernatants were assayed for IL-1beta, IL-6, and TNF-alpha by ELISA. Peak sarcomere shortening was decreased in the burn group at 1, 6, 12, and 24 h after burn. IL-1beta, IL-6, and TNF-alpha levels were increased in cardiomyocytes isolated 1 h after burn compared with sham controls, but returned to sham levels at 6, 12, and 24 h after burn. LPS exposure caused dose-dependent decreases in sarcomere shortening in sham and burn animals. LPS exposure did not produce increased cardiomyocyte cytokine expression. Burn injury diminished peak sarcomere shortening. Whereas exposure to LPS did not have an effect on cardiomyocyte cytokine expression, LPS significantly inhibited sarcomere shortening in a dose-dependent fashion. Combined burn and LPS exposure inhibited sarcomere shortening more than each alone. These results demonstrate that LPS exposure and burn injury independently decrease peak cardiac shortening. These decreases did not directly correlate with the levels of cytokines released in response to each stressor.

show abstract

“…The study showed a slight decrease of several C components (C3, C4, and factor B) and a transient consumption coagulopathy. Of particular interest in the latter paper, the authors presented direct hemodynamic and laboratory evidence for pulmonary capillary leakage as the underlying cause of edema, a process known to arise as a consequence of C activation-related sequestration of granulocytes and platelets in the pulmonary microcirculation [28][29][30]. Another case report postulated that C activation was responsible for the death of a patient undergoing IV pyelography with diatrizoate [10].…”

Section: Complement Activation As An Underlying Cause Of Radiocontrasmentioning

confidence: 99%

Hypersensitivity reactions to radiocontrast media: The role of complement activation

Szebeni

2004

Curr Allergy Asthma Rep

View full text Add to dashboard Cite

Although intravenous use of radiocontrast media (RCM) for a variety of radiographic procedures is generally safe, clinically significant acute hypersensitivity reactions still occur in a significant percentage of patients. The mechanism of these anaphylactoid, or "pseudoallergic," reactions is complex, involving complement activation, direct degranulation of mast cells and basophils, and modulation of enzymes and proteolytic cascades in plasma. In this review, basic information on different RCMs and their reactogenicity is summarized and updated, and the prevalence, pathomechanism, prediction, prevention, treatment, and economic impact of hypersensitivity reactions are discussed. Particular attention is paid to the in vitro and in vivo evidence supporting complement activation as an underlying cause of RCM reactions.

show abstract

REQUIREMENT FOR C5a IN LUNG VASCULAR INJURY FOLLOWING THERMAL TRAUMA TO RAT SKIN

Cited by 30 publications

References 0 publications

C5a-Blockade Improves Burn-Induced Cardiac Dysfunction

C5a-Blockade Improves Burn-Induced Cardiac Dysfunction

Cardiomyocyte Function After Burn Injury and Lipopolysaccharide Exposure: Single-Cell Contraction Analysis and Cytokine Secretion Profile

Hypersensitivity reactions to radiocontrast media: The role of complement activation

Contact Info

Product

Resources

About