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sCR1sLe ameliorates ischemia/reperfusion injury in experimental lung transplantation.
J Thorac Cardiovasc Surg. 2000 Dec; 120(6):1078-84.JT

Abstract

BACKGROUND

The nonspecific immune response with activation of the complement system and polymorphonuclear leukocytes is important for the mediation of reperfusion injury after lung transplantation. In this study, we investigated the combined blockade of the complement system and leukocyte adhesion by a novel drug combining soluble complement receptor type 1 (sCR1, CD35) with the selectin ligand sialyl Lewis X (sLe(X), CD15s) synthesized to sCR1sLe(X). Both sCR1 and sCR1sLe(X) were supplied by AVANT Immunotherapeutics, Inc, Needham, Massachusetts.

METHODS

Orthotopic allogeneic single left lung transplantation was performed in male rats (Brown Norway to Fischer F344; n = 5 in all groups) after a total ischemic time of 20 hours. Recipients received either no specific treatment (control) or administration of sCR1 (10 mg/kg) or sCR1sLe(X) (10 mg/kg) 15 minutes before reperfusion by intracardiac injection. Twenty-four hours after reperfusion, the native contralateral lung was occluded to assess gas exchange of the graft only. In additional animals (5 per group), lung tissue was frozen 24 hours after reperfusion and assessed for myeloperoxidase activity as a measurement of neutrophil migration into the graft and thiobarbituric acid reactive substances to quantify lipid peroxidation.

RESULTS

Graft function as assessed by arterial PO (2) in recipients treated with sCR1sLeX was superior not only to that of controls (383 +/- 53 vs 56 +/- 7 mm Hg, P =. 000095) but also to that of animals treated with sCR1 (243 +/- 45 mm Hg, P =.031). This improvement was confirmed by significant reduction of neutrophil migration (0.33 +/- 0.05 vs control, 1.0 +/- 0.09 DeltaOD/mg/min, P =.0000024) and lipid peroxidation (6.2 +/- 0. 38 vs control, 10.6 +/- 0.54 pmol/g, P =.00021).

CONCLUSIONS

Our data indicate that combined inhibition of complement activation and leukocyte adhesion with sCR1sLe(X) reduces reperfusion injury significantly and that both mechanisms are effectively inhibited in this model.

Authors+Show Affiliations

Division of General Thoracic Surgery, University Hospital, Berne, Switzerland.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11088029

Citation

Stammberger, U, et al. "SCR1sLe Ameliorates Ischemia/reperfusion Injury in Experimental Lung Transplantation." The Journal of Thoracic and Cardiovascular Surgery, vol. 120, no. 6, 2000, pp. 1078-84.
Stammberger U, Hamacher J, Hillinger S, et al. SCR1sLe ameliorates ischemia/reperfusion injury in experimental lung transplantation. J Thorac Cardiovasc Surg. 2000;120(6):1078-84.
Stammberger, U., Hamacher, J., Hillinger, S., & Schmid, R. A. (2000). SCR1sLe ameliorates ischemia/reperfusion injury in experimental lung transplantation. The Journal of Thoracic and Cardiovascular Surgery, 120(6), 1078-84.
Stammberger U, et al. SCR1sLe Ameliorates Ischemia/reperfusion Injury in Experimental Lung Transplantation. J Thorac Cardiovasc Surg. 2000;120(6):1078-84. PubMed PMID: 11088029.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - sCR1sLe ameliorates ischemia/reperfusion injury in experimental lung transplantation. AU - Stammberger,U, AU - Hamacher,J, AU - Hillinger,S, AU - Schmid,R A, PY - 2000/11/23/pubmed PY - 2001/2/28/medline PY - 2000/11/23/entrez SP - 1078 EP - 84 JF - The Journal of thoracic and cardiovascular surgery JO - J Thorac Cardiovasc Surg VL - 120 IS - 6 N2 - BACKGROUND: The nonspecific immune response with activation of the complement system and polymorphonuclear leukocytes is important for the mediation of reperfusion injury after lung transplantation. In this study, we investigated the combined blockade of the complement system and leukocyte adhesion by a novel drug combining soluble complement receptor type 1 (sCR1, CD35) with the selectin ligand sialyl Lewis X (sLe(X), CD15s) synthesized to sCR1sLe(X). Both sCR1 and sCR1sLe(X) were supplied by AVANT Immunotherapeutics, Inc, Needham, Massachusetts. METHODS: Orthotopic allogeneic single left lung transplantation was performed in male rats (Brown Norway to Fischer F344; n = 5 in all groups) after a total ischemic time of 20 hours. Recipients received either no specific treatment (control) or administration of sCR1 (10 mg/kg) or sCR1sLe(X) (10 mg/kg) 15 minutes before reperfusion by intracardiac injection. Twenty-four hours after reperfusion, the native contralateral lung was occluded to assess gas exchange of the graft only. In additional animals (5 per group), lung tissue was frozen 24 hours after reperfusion and assessed for myeloperoxidase activity as a measurement of neutrophil migration into the graft and thiobarbituric acid reactive substances to quantify lipid peroxidation. RESULTS: Graft function as assessed by arterial PO (2) in recipients treated with sCR1sLeX was superior not only to that of controls (383 +/- 53 vs 56 +/- 7 mm Hg, P =. 000095) but also to that of animals treated with sCR1 (243 +/- 45 mm Hg, P =.031). This improvement was confirmed by significant reduction of neutrophil migration (0.33 +/- 0.05 vs control, 1.0 +/- 0.09 DeltaOD/mg/min, P =.0000024) and lipid peroxidation (6.2 +/- 0. 38 vs control, 10.6 +/- 0.54 pmol/g, P =.00021). CONCLUSIONS: Our data indicate that combined inhibition of complement activation and leukocyte adhesion with sCR1sLe(X) reduces reperfusion injury significantly and that both mechanisms are effectively inhibited in this model. SN - 0022-5223 UR - https://www.unboundmedicine.com/medline/citation/11088029/sCR1sLe_ameliorates_ischemia/reperfusion_injury_in_experimental_lung_transplantation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022522300473174 DB - PRIME DP - Unbound Medicine ER -