Moderation of skeletal muscle reperfusion injury by a sLex-glycosylated complement inhibitory protein

2001 ◽  
Vol 281 (1) ◽  
pp. C224-C230 ◽  
Author(s):  
Constantinos Kyriakides ◽  
Yong Wang ◽  
William G. Austen ◽  
Joanne Favuzza ◽  
Lester Kobzik ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Reperfusion Injury ◽  
Vascular Endothelium ◽  
Hindlimb Ischemia ◽  
Permeability Index ◽  
Inhibitory Protein ◽  
Sialyl Lewis ◽  
Neutrophil Depletion

The role of the sialyl Lewisx(sLex)-decorated version of soluble complement receptor type 1 (sCR1) in moderating skeletal muscle reperfusion injury, by antagonizing neutrophil endothelial selectin interaction and complement activation, is examined. Mice underwent 2 h of hindlimb ischemia and 3 h of reperfusion. Permeability index (PI) was assessed by extravasation of125I-labeled albumin. Neutrophil depletion and complement inhibition with sCR1 reduced permeability by 72% (PI 0.81 ± 0.10) compared with a 42% decrease (PI 1.53 ± 0.08) observed in neutropenic mice, indicating that part of the complement-mediated injury is neutrophil independent. sCR1sLextreatment reduced PI by 70% (PI 0.86 ± 0.06), an additional 20% decrease compared with sCR1 treatment (PI 1.32 ± 0.08). Treatment with sCR1sLex0.5 and 1 h after reperfusion reduced permeability by 63% (PI 0.09 ± 0.07) and 52% (PI 1.24 ± 0.09), respectively, compared with the respective decreases of 41% (PI 1.41 ± 0.10) and 32% (PI 1.61 ± 0.07) after sCR1 treatment. Muscle immunohistochemistry stained for sCR1 only on the vascular endothelium of sCR1sLex-treated mice. In conclusion, sCR1sLexis more effective than sCR1 in moderating skeletal muscle reperfusion injury.

scholarly journals Skeletal muscle reperfusion injury is mediated by neutrophils and the complement membrane attack complex

1999 ◽  
Vol 277 (6) ◽  
pp. C1263-C1268 ◽  
Author(s):  
Constantinos Kyriakides ◽  
William Austen ◽  
Yong Wang ◽  
Joanne Favuzza ◽  
Lester Kobzik ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Reperfusion Injury ◽  
Membrane Attack Complex ◽  
Wild Type ◽  
Complement Components ◽  
Neutrophil Activity ◽  
Deficient Mice ◽  
Terminal Complement

The relative inflammatory roles of neutrophils, selectins, and terminal complement components are investigated in this study of skeletal muscle reperfusion injury. Mice underwent 2 h of hindlimb ischemia followed by 3 h of reperfusion. The role of neutrophils was defined by immunodepletion, which reduced injury by 38%, as did anti-selectin therapy with recombinant soluble P-selectin glycoprotein ligand-immunoglobulin (Ig) fusion protein. Injury in C5-deficient and soluble complement receptor type 1-treated wild-type mice was 48% less than that of untreated wild-type animals. Injury was restored in C5-deficient mice reconstituted with wild-type serum, indicating the effector role of C5–9. Neutropenic C5-deficient animals showed additive reduction in injuries (71%), which was lower than C5-deficient neutrophil-replete mice, indicating neutrophil activity without C5a. Hindlimb histological injury was worse in ischemic wild-type and C5-deficient animals reconstituted with wild-type serum. In conclusion, the membrane attack complex and neutrophils act additively to mediate skeletal muscle reperfusion injury. Neutrophil activity is independent of C5a but is dependent on selectin-mediated adhesion.

scholarly journals Effects of alprostadil and iloprost on renal, lung, and skeletal muscle injury following hindlimb ischemia–reperfusion injury in rats

2016 ◽  
Vol Volume 10 ◽  
pp. 2651-2658 ◽  
Author(s):  
Mustafa Arslan ◽  
Dilek Erer ◽  
Abdullah Özer ◽  
Huseyin Demirtas ◽  
İpek Isık Gonul ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Reperfusion Injury ◽  
Muscle Injury ◽  
Hindlimb Ischemia ◽  
Skeletal Muscle Injury

Selective Neutrophil Depletion with Monoclonal Antibodies Attenuates Ischemia/Reperfusion Injury in Skeletal Muscle

1998 ◽  
Vol 14 (02) ◽  
pp. 109-116 ◽  
Author(s):  
Yusuke Iwahori ◽  
Naoki Ishiguro ◽  
Takuya Shimizu ◽  
Seiji Kondo ◽  
Yuichiro Yabe ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Monoclonal Antibodies ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Neutrophil Depletion

Role of leucocytes in damage to the vascular endothelium during ischaemia-reperfusion injury

2006 ◽  
Vol 63 (4) ◽  
pp. 166-170 ◽  
Author(s):  
S.F. Hughes ◽  
M.J. Cotter ◽  
S.A. Evans ◽  
K.P. Jones ◽  
R.A. Adams
Keyword(s):  
Reperfusion Injury ◽  
Vascular Endothelium ◽  
Ischaemia Reperfusion Injury ◽  
Ischaemia Reperfusion

scholarly journals Angiotensin Receptor Type 1 Inhibition in Lymphopenia and in Neutropenia After Traumatic Brain Injury In Mice: a Randomized Controlled Study (ATLANTIS)

2021 ◽  
Author(s):  
Ralph Timaru-Kast ◽  
Shila P. Coronel-Castello ◽  
Tobias Krämer ◽  
André V. Hugonnet ◽  
Michael K.E. Schäfer ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Damage ◽  
Receptor Type ◽  
Wild Type ◽  
Secondary Brain Damage ◽  
Neutrophil Depletion ◽  
Cerebral Inflammation

Abstract Background: Cerebral inflammation with invasion of neutrophils and lymphocytes is an important factor in the process of secondary brain damage expansion after traumatic brain injury (TBI). Depletion of neutrophils in mice has been shown to reduce neurologic impairment after TBI. The intrinsic cerebral renin-angiotensin system is an important mediator of cerebral inflammation, as inhibition of the angiotensin II receptor type 1 (AT1) with candesartan improves neurologic recovery, and reduces secondary brain damage and cerebral neutrophil invasion after TBI. The present study was therefore designed to determine the role of immune cells in AT1 inhibition-mediated neuroprotection after TBI. Methods: In study A we assessed the effect of neutrophil depletion in mice after TBI. In study B we investigated the impact of RAG1 deficiency (RAG1-/-; mice without mature B- and T-lymphocytes) after TBI. In study C we investigated the role of neutrophils in candesartan mediated protection after TBI in wild-type mice with and without neutrophil depletion. In study D we examined the role of lymphocytes in AT1 inhibition mediated neuroprotection after TBI in RAG1-/-.Results: Neutropenic and RAG1-/- mice showed reduced brain damage compared to control groups. In control antibody treated wild type mice AT1 inhibition reduced lesion volumes and inflammation compared to vehicle, while in neutropenic mice, candesartan had no effect. In RAG1-/- mice AT1 inhibition resulted in reduction of brain damage and neuroinflammation compared to vehicle group. Conclusion: The present results demonstrate, that reduction of neutrophils and of lymphocytes as well as AT1 inhibition in wild type and RAG1-/- mice reduce brain damage and inflammation after TBI. However, AT1 inhibition was neuroprotective in RAG1-/- mice, but not in neutropenic mice. Therefore, the results indicate that AT1 inhibition mediated neuroprotection may be exerted by anti-inflammatory effects on neutrophils, with a subsequent reduction of neutrophil invasion.

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