The relationship of ischemia-reperfusion injury of transplanted lung and the up- regulation of major histocompatibility complex II on host peripheral

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The relationship of ischemia-reperfusion injury of transplanted lung and the upregulation of major histocompatibility complex II on host peripheral A.K. Qayumi, MD, PhD, M. Nikbakht-Sangari, BSc, D.V. Godin, PhD, J.C. English, MD, K.J. Horley, PhD, P.A. Keown, MD, S.P. Lim, MD, PhD, D.M. Ansley, MD, M.S. Koehle, MSc The Journal of Thoracic and Cardiovascular Surgery Volume 115, Issue 5, Pages 978-989 (May 1998) DOI: 10.1016/S0022-5223(98)70395-2 Copyright © 1998 Mosby, Inc. Terms and Conditions

Fig. 1 Lung function parameters. Percent changes of Po2 (a), alveolar-arterial oxygen gradient (b), alveolar-arterial oxygen ratio (c), and volume/pressure relationships (d) are shown. The solid line represents group A (4 hours of cold ischemia); the dashed line represents group B (15 hours of cold ischemia); and the dotted line represents group C (2 hours of warm ischemia). P values with an asterisk indicate significant differences within groups, and those with a diamond sign indicate significant differences between groups. pre, Before transplantation; 30m post, 30 minutes after reperfusion; 72h post, 72 hours after reperfusion. The Journal of Thoracic and Cardiovascular Surgery 1998 115, 978-989DOI: (10.1016/S0022-5223(98)70395-2) Copyright © 1998 Mosby, Inc. Terms and Conditions

Fig. 2 Tissue antioxidant enzyme activities. Means ± standard errors of SOD (a), catalase (b), GRed (c), and GPx (d) are shown before transplantation (plain bars) and after transplantation (hatched bars). Group A, 4 hours of cold ischemia); group B, 15 hours of cold ischemia; and group C, 2 hours of warm ischemia. P values were derived from paired t tests at 95% confidence level of before and after measurements. The Journal of Thoracic and Cardiovascular Surgery 1998 115, 978-989DOI: (10.1016/S0022-5223(98)70395-2) Copyright © 1998 Mosby, Inc. Terms and Conditions

Fig. 3 Plasma cytokine levels. Percent changes of IL-2 (a), IL-4 (b), IL-10 (c), and TNF-α (d) are shown. The solid line represents group A; the dashed line represents group B; and the dotted line represents group C. P values with an asterisk depict significant differences within groups, and those with a diamond sign depict significant differences between groups. pre, Before transplantation; 30m post, 30 minutes after reperfusion; 72h post, 72 hours after reperfusion. The Journal of Thoracic and Cardiovascular Surgery 1998 115, 978-989DOI: (10.1016/S0022-5223(98)70395-2) Copyright © 1998 Mosby, Inc. Terms and Conditions

Fig. 4 Expression of MHC II HLA-DR-β on CD3+ host peripheral lymphocytes. a, MHC II HLA-DR-β intensity per MHC+ CD3+ cell. b, The number of host peripheral lymphocytes (B and T cells). The solid line represents group A; the dashed line represents group B, and the dotted line represents group C. P values were derived by nonparametric Mann/Whitney tests. c, Regression analysis of MHC II intensity per cell versus ischemic time. d, An example of a bitmap generated by flow cytometry analysis – quadrant 2 denotes MHC+ CD3+ cells. pre, Before transplantation; 24h post, 24 hours after reperfusion; 48h post, 48 hours after reperfusion; 72h post, 72 hours after reperfusion; PE, phycoerythrin; FITC, fluorescein isothiocyanate; 2h post, 2 hours after reperfusion. The Journal of Thoracic and Cardiovascular Surgery 1998 115, 978-989DOI: (10.1016/S0022-5223(98)70395-2) Copyright © 1998 Mosby, Inc. Terms and Conditions

Fig. 5 Histologic comparison of lung tissue from allografts undergoing 4 hours (a) and 15 hours (b) cold ischemic preservation time, and 2 hours of warm, in situ ischemia (c). a, Expansion of the interlobular septal tissue by lymphatic dilation (L) and tissue edema (*). There is a sparse alveolar infiltrate (arrow). b, Alveolar infiltrates are more dense (*) and are composed of mononuclear and polymorphonuclear inflammatory cells. c, Foci of acute alveolar hemorrhage are seen (arrow), in addition to the inflammatory infiltrate. (Hematoxylin and eosin; original magnification ×125, all panels. The Journal of Thoracic and Cardiovascular Surgery 1998 115, 978-989DOI: (10.1016/S0022-5223(98)70395-2) Copyright © 1998 Mosby, Inc. Terms and Conditions

Fig. 6 Immunohistochemistry of lungs undergoing 2 hours of warm in situ ischemia: a, preischemic biopsy; b, lung at time of death. In a, basal, or constituitive expression of MHC II is identified on vascular endothelium (arrow); there is no alveolar inflammatory infiltrate (*). In b, there is a large increase in MHC II tissue expression contributed to by an influx of MHC II+ inflammatory cells and increased expression of MHC II on capillary and larger vessel endothelium (arrow). (Hematoxylin and eosin; original magnification ×125, both panels.) The Journal of Thoracic and Cardiovascular Surgery 1998 115, 978-989DOI: (10.1016/S0022-5223(98)70395-2) Copyright © 1998 Mosby, Inc. Terms and Conditions

Fig. 7 Immunohistochemistry of lungs undergoing 4 hours of cold, ex vivo preservation before implantation. a, Tissue before transplantation shows low basal expression of MHC II antigen on vascular endothelium (arrow). b, In tissue after transplantation, endothelial MHC II expression is increased (arrow). (Hematoxylin and eosin; original magnification ×125, both panels.) The Journal of Thoracic and Cardiovascular Surgery 1998 115, 978-989DOI: (10.1016/S0022-5223(98)70395-2) Copyright © 1998 Mosby, Inc. Terms and Conditions