Innate-Adaptive Immune Responses in Organ Ischemia/Reperfusion Injury

2013 ◽  
pp. 29-34
Author(s):  
Haofeng Ji ◽  
Yuan Zhai ◽  
Jerzy W. Kupiec-Weglinski
Keyword(s):  
Immune Responses ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Adaptive Immune Responses ◽  
Adaptive Immune

Two-Photon Imaging of Immune Cell Dynamics: Moving from 2D Fixed Tissue Sections to 3D Dynamic Histology In Vivo

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. SCI-24-SCI-24
Author(s):  
Mark J. Miller
Keyword(s):  
Immune Responses ◽  
Bacterial Infection ◽  
Reperfusion Injury ◽  
Immune Cell ◽  
Ischemia Reperfusion Injury ◽  
Inflammatory Diseases ◽  
Ischemia Reperfusion ◽  
Neutrophil Recruitment ◽  
Neutrophil Extravasation

Abstract Cell-mediated immune responses are highly dependent on environmental context, thus making in vivo studies an important complement to in vitro and molecular approaches. Two-photon microscopy (2PM) is a fluorescence based imaging approach that allows single-cell dynamics to be studied directly in their 3D native tissue context. 2PM is an ideal approach for analyzing leukocyte trafficking dynamics quantitatively and testing cellular immune mechanisms in vivo. Several example applications will be presented where 2PM has uncovered novel immunological phenomena and provided fresh insight into immune responses to infection, autoimmunity and cancer. While 2P imaging has been used extensively to study immune cell trafficking and function in mice, progress is being made to use this imaging technique on clinical biopsy specimens to acquire a multi-dimensional picture of human tissue pathology. We used in vivo 2PM in pre-clinical models of arthritis and bacterial infection to compare and contrast the role of monocytes on neutrophil recruitment. The rapid recruitment of neutrophils and monocytes is critical to early host immune responses to bacterial infection. However, leukocyte recruitment also contributes to chronic inflammatory diseases such as human rheumatoid arthritis. Understanding how cell recruitment is regulated in different inflammatory contexts is crucial for developing safe and effective anti-inflammatory therapies. We found that monocyte depletion with clodronate-liposomes prevented arthritis development in a modified K/BxN serum transfer arthritis model. This protective effect was associated with significantly reduced neutrophil transendothelial migration efficiency. Furthermore, single-cell tracking of a minor population of extravasated neutrophils showed that neutrophil migration and chemotaxis in interstitial tissues was disrupted, contributing to decreased cell localization at phalangeal joints. Similar results were obtained when CCR2+ monocytes were depleted selectively using the monoclonal antibody MC-21, thus implicating CCR2+ monocytes as key regulators of neutrophil extravasation during arthritis initiation. In contrast, neutrophil recruitment to subcutaneous bacterial challenge remained intact and neutrophil extravasation and chemotaxis to sites of infection was not significantly different as compared to non-depleted controls. We also examined whether neutrophil extravasation during acute pulmonary inflammation required monocytes. Neutrophil recruitment in vivo was assessed in a mouse lung transplant-mediated ischemia reperfusion injury model. Similar to the results in the arthritis model, neutrophil recruitment in response to ischemia reperfusion injury was also monocyte dependent. In addition, Ccr2 knockout recipient mice were protected for ischemia reperfusion injury. Results from these complementary mouse models implicate CCR2+ monocytes as key regulators of neutrophil extravasation and chemotaxis in under conditions of aseptic inflammation and further suggest that the cell recruitment signals that that operate during bacterial infection may be quantitatively and/or qualitatively distinct. These studies raise the intriguing possibility that targeting monocytes during chronic inflammatory diseases such as rheumatoid arthritis or acute inflammatory conditions such as ischemia reperfusion injury might provide safer and more selective anti-inflammatory therapies than those that target neutrophils directly. Disclosures: No relevant conflicts of interest to declare.

Cardiomyocyte-specific Bcl-2 overexpression attenuates ischemia-reperfusion injury, immune response during acute rejection, and graft coronary artery disease

Blood ◽  
2004 ◽  
Vol 104 (12) ◽  
pp. 3789-3796 ◽  
Author(s):  
Masashi Tanaka ◽  
Susumu Nakae ◽  
Raya D. Terry ◽  
Golnaz K. Mokhtari ◽  
Feny Gunawan ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Acute Rejection ◽  
Immune Responses ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cardiac Allografts ◽  
Artery Disease

After cardiac transplantation, graft damage occurs secondary to ischemia-reperfusion injury and acute rejection. This damage ultimately leads to the development of graft coronary artery disease (GCAD), which limits long-term graft survival. Apoptosis is directly involved in graft injury, contributing to the development of GCAD. To assess the role of the antiapoptotic factor Bcl-2 in the process of GCAD, we transplanted hearts from FVB transgenic mice overexpressing human Bcl-2 under the control of α-myosin heavy chain promoter into allogenic C57BL/6 mice. Bcl-2 overexpression led to reduced cytochrome c–mediated caspase-9–dependent cardiomyocyte apoptosis and local inflammation (neutrophil infiltration and proinflammatory cytokine production) in cardiac allografts during ischemia-reperfusion injury and also led to reduced immune responses (inflammatory cell infiltration, production of TH1 cytokines and chemokines, and expression of adhesion molecules) during acute and chronic rejection without affecting host CD4+ and CD8+ cell responses in the spleen. Thus, local Bcl-2 expression directly contributes to the modulation of local immune responses in allograft rejection, resulting in attenuated GCAD. In conclusion, our findings suggest that the modulation of Bcl-2 expression by pharmacologic up-regulation or gene transfer may be of clinical benefit in the short- and long-term function of cardiac allografts.

scholarly journals The Microbiome, Systemic Immune Function, and Allotransplantation

2015 ◽  
Vol 29 (1) ◽  
pp. 191-199 ◽  
Author(s):  
Anoma Nellore ◽  
Jay A. Fishman
Keyword(s):  
Immune Responses ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Community Based ◽  
Adaptive Immune ◽  
Reciprocal Interactions ◽  
And Control ◽  
Diverse Interactions

SUMMARYDiverse effects of the microbiome on solid organ transplantation are beginning to be recognized. In allograft recipients, microbial networks are disrupted by immunosuppression, nosocomial and community-based infectious exposures, antimicrobial therapies, surgery, and immune processes. Shifting microbial patterns, including acute infectious exposures, have dynamic and reciprocal interactions with local and systemic immune systems. Both individual microbial species and microbial networks have central roles in the induction and control of innate and adaptive immune responses, in graft rejection, and in ischemia-reperfusion injury. Understanding the diverse interactions between the microbiome and the immune system of allograft recipients may facilitate clinical management in the future.

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