Pathogenic Natural Antibodies Recognizing Annexin IV Are Required to Develop Intestinal Ischemia-Reperfusion Injury
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA112027 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Intestinal ischemia-reperfusion (IR) injury is initiated when natural IgM antibodies recognize neo-epitopes that are revealed on ischemic cells. The target molecules and mechanisms whereby these neo-epitopes become accessible to recognition are not well understood. Proposing that isolated intestinal epithelial cells (IEC) may carry IR-related neo-epitopes, we used in vitro IEC binding assays to screen hybridomas created from B cells of unmanipulated wild type C57BL/6 mice. We identified a novel IgM monoclonal antibody (mAb B4) that reacted with the surface of IEC by flow cytometric analysis and was alone capable of causing complement activation, neutrophil recruitment and intestinal injury in otherwise IR-resistant Rag1-/- mice. Monoclonal Ab B4 was found to specifically recognize mouse annexin IV. Pre-injection of recombinant annexin IV blocked IR injury in wild type C57BL/6 mice, demonstrating the requirement for recognition of this protein in order to develop IR injury in the context of a complex natural antibody repertoire. Humans were also found to exhibit IgM natural antibodies that recognize annexin IV. These data in toto identify annexin IV as a key ischemia-related target antigen that is recognized by natural Abs in a pathologic process required in vivo to develop intestinal IR injury. Keywords: Natural antibodies, Annexin, Ischemia Reperfusion, Inflammation, Complement In the study presented here, a total of 4 custom spotted antigen slides were hybridized with known antibodies.
2010-05-05 | E-GEOD-14862 | biostudies-arrayexpress
Project description:Intestinal ischemia-reperfusion (IR) injury is initiated when natural IgM antibodies recognize neo-epitopes that are revealed on ischemic cells. The target molecules and mechanisms whereby these neo-epitopes become accessible to recognition are not well understood. Proposing that isolated intestinal epithelial cells (IEC) may carry IR-related neo-epitopes, we used in vitro IEC binding assays to screen hybridomas created from B cells of unmanipulated wild type C57BL/6 mice. We identified a novel IgM monoclonal antibody (mAb B4) that reacted with the surface of IEC by flow cytometric analysis and was alone capable of causing complement activation, neutrophil recruitment and intestinal injury in otherwise IR-resistant Rag1-/- mice. Monoclonal Ab B4 was found to specifically recognize mouse annexin IV. Pre-injection of recombinant annexin IV blocked IR injury in wild type C57BL/6 mice, demonstrating the requirement for recognition of this protein in order to develop IR injury in the context of a complex natural antibody repertoire. Humans were also found to exhibit IgM natural antibodies that recognize annexin IV. These data in toto identify annexin IV as a key ischemia-related target antigen that is recognized by natural Abs in a pathologic process required in vivo to develop intestinal IR injury. Keywords: Natural antibodies, Annexin, Ischemia Reperfusion, Inflammation, Complement
2009-02-19 | GSE14862 | GEO
Project description: Not available
| S-EPMC2820395 | biostudies-literature
Project description:Ischemia-reperfusion (IR) injury, a ubiquitous consequence of liver transplantation, is a cause of early graft rejection and increased morbidity. At present, there are no effective strategies to reduce hepatic IR injury. Molecular mechanisms that promote cell survival under these circumstances are largely undefined. We examined changes in global gene expression at early reperfusion times to identify potential IR-mediated protective responses. Using a rat model of 30 minutes of 70% warm ischemia followed by reperfusion, RNA for microarray analysis was extracted from the non-ischemic and the ischemic-reperfused lobes at four reperfusion times: 0 (no reperfusion), 0.5, 2, and 6 hours. Differentially expressed genes and pathway analyses were used to identify IR-induced events. The transcriptome of the reperfused lobes was unique and discrete at each reperfusion time, showing no evidence of sustained changes of the gene expression alterations seen at 30 minutes of reperfusion. At all reperfusion times, a significant portion of gene expression changes in the reperfused lobes were present in the non-ischemic lobes. However, the earliest reperfusion time, 30 minutes, showed a marked increase in the expression of a set of immediate-early genes (c-Fos, c-Jun, Atf3, Egr1) that was exclusive to the reperfused lobe. Similarities of gene expression changes in the reperfused and the non-ischemic lobes at each time suggest that hemodynamics and/or circulating factors are potent stimuli in an IR model. However, early reperfusion events appear to reflect a cell-autonomous response that may be protective, thereby representing potential targets to ameliorate IR injury.
2019-12-16 | GSE117915 | GEO
Project description:To examine the protective effect of B12 on myocardial ischemia/reperfusion injury and figure out the mechanism of B12.
2024-01-01 | GSE225105 | GEO
Project description:To identify the role of mRNA during myocardial ischemia-reperfusion in mice, we have employed high-throughput sequencing to detect mRNA expression. Samples were collected from the control group and the ischemia reperfusion groups , with 5 samples per group. The candidate mRNA that may affect the process of myocardial ischemia-reperfusion was screened by comparing the ischemia-reperfusion group and the control group.
2023-11-15 | GSE223343 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE21405: MicroRNA Profiling In Ischemia-Reperfusion Injury Of The Gracilis Muscle In Rats GSE21406: Potential Target Genes of MicroRNA-21 In Ischemia-Reperfusion Injury Of The Gracilis Muscle In Rats Refer to individual Series
2010-04-22 | E-GEOD-21423 | biostudies-arrayexpress
Project description:Stroke is the fifth leading cause of death in the United States and is a leading cause of serious long-term disability worldwide. Innate immune responses are critical in stroke pathophysiology, and microglia are key cellular effectors in the CNS response to ischemia/reperfusion. Using a transcriptional analysis approach, we identified a robust interferon (IFN)-stimulated gene response within microglia exposed to ischemia/reperfusion. We have demonstrated that these responses are dependent on innate immune signaling components including Toll-like receptor-4 and type I IFNs. We have also elucidated several novel ischemia/reperfusion-induced microglial signaling mechanisms.
2020-04-01 | GSE107983 | GEO
Project description:The heart of late pregnant (LP) rodents is more prone to ischemia/reperfusion (I/R) injury compared to non-pregnant rodents. We hypothesized that Intralipid (ITLD) protects the heart in LP rodents against I/R injury. We performed genome-wide expression profiling to identify the underlying mechanisms. Female LP rat hearts were subjected to ischemia followed by reperfusion with vehicle or ITLD (one bolus of 5mg/kg).
2016-02-09 | E-GEOD-77698 | biostudies-arrayexpress
Project description:To examine the age-related vulnerability to lung ischemia reperfusion injury, pulmonary gene expression profiles after lung ischemia reperfusion were compared between young and old mice.
2024-04-06 | GSE211951 | GEO