Intracapillary leucocyte accumulation as a novel antihaemorrhagic mechanism in acute pancreatitis in mice

Ryschich, Eduard; Kerkadze, Vachtang; Deduchovas, Olegas; Salnikova, Olga; Parseliunas, A.; Märten, Angela; Hartwig, Werner; Sperandio, Markus; Schmidt, Jan

doi:10.1136/gut.2008.170001

Cited by 17 publications

(14 citation statements)

References 52 publications

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“…They control intravascular leukocyte crawling and transmigration by interaction with endothelial ICAM‐1 adhesion molecules 10, 11. It has been shown that the inhibition or knockout of β 2 ‐integrins as well as of ICAM‐1 strongly affects leukocyte recruitment into the inflamed pancreatic12, 13 and non‐pancreatic tissue 14, 15. In the liver, ICAM‐1 is not always mandatory for leukocyte recruitment and depends on the kind of inflammatory stimulus 16, 17.…”

mentioning

confidence: 99%

α_Lβ₂ Integrin is indispensable for CD8⁺ T‐cell recruitment in experimental pancreatic and hepatocellular cancer

Takeichi

Mocevicius

Deduchovas

et al. 2011

Intl Journal of Cancer

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Recruitment of activated leukocytes from peripheral blood into the tumor tissue is a crucial step of the immune response, which is controlled by the interaction between specific adhesion molecules such as endothelial ICAM-1 and leukocyte b 2 -integrins. Although attenuated expression of adhesion molecules on tumor endothelium has been proposed to represent a mechanism, which suppresses the intratumoral leukocyte infiltration, the relevance of adhesion molecules for leukocyte recruitment in tumor tissue is poorly understood. The present study is the first investigation of the role of ICAM-1 and b 2 -integrins in leukocyte recruitment in pancreatic and hepatocellular cancer in vivo, which was studied using knockout mice, intravital time-lapse microscopy and immunohistochemistry. We found that tumor tissue of both pancreatic and hepatocellular cancer was infiltrated with numerous active lymphoid and myeloid leukocytes, although the leukocyte extravasation rate in tumor blood vessels was very low. The knockout of LFA-1 (also known as a L b 2 integrin) strongly suppressed recruitment of CD8 1 T cells whereas no significant differences of leukocyte adhesion and infiltration were found in ICAM-1 2/2 and Mac-1mice. Analysis of the interstitial leukocyte migration demonstrated that intratumoral leukocytes used haptokinetic type of migration, however, no significant differences of leukocyte migration between any knockout strains were found. We concluded that leukocyte recruitment in pancreatic and hepatocellular cancer is a slow-going process whose dynamics clearly contrasts to a high-speed leukocyte recruitment during acute inflammation. In contrast to acute inflammatory reaction, only LFA-1 controls recruitment of CD8 1 T-cells in both pancreatic and hepatocellular cancer, whereas ICAM-1 and Mac-1 are dispensable.Pancreatic and hepatocellular cancer remain an extremely aggressive malignancies with a poor prognosis. 1 The mean 5-year survival is 6% and 14% for pancreatic and liver cancer, respectively.

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mentioning

confidence: 99%

α_Lβ₂ Integrin is indispensable for CD8⁺ T‐cell recruitment in experimental pancreatic and hepatocellular cancer

Takeichi

Mocevicius

Deduchovas

et al. 2011

Intl Journal of Cancer

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“…Triggered by chemotactic signals, leukocytes arrest on the vascular endothelium and prepare for their migration into tissue 24. Ryschich et al 7. demonstrated that intracapillary leukocyte accumulation represents an initial step of leukocyte activation during AP, consisting of the rapid promotion of leukocyte adhesion to the capillary endothelium and the intraluminal intracapillary crawling of leukocytes, which leads to sustained capillary occlusion.…”

Section: Discussionmentioning

confidence: 99%

“…Acinar cell injury leads to a local inflammatory reaction with inflammatory leukocyte infiltration 6. Intracapillary leukocyte accumulation represents an initial step of leukocyte activation during AP 7. Once recruited, activated leukocytes aggravate the local damage of the pancreatic tissue by releasing inflammatory cytokines 6,8.…”

Section: Introductionmentioning

confidence: 99%

CD64 Expression Is Increased in Patients with Severe Acute Pancreatitis: Clinical Significance

Zhang¹,

Ling²,

Wu³

et al. 2014

Gut Liver

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Background/AimsUpregulated CD64 expression on neutrophils is the most useful marker for acute bacterial infections and systemic inflammation. However, it is unknown whether CD64 is involved in the pathogenesis of acute pancreatitis (AP). This study was designed to determine whether CD64 is implicated in severe acute pancreatitis (SAP), and thus, is a suitable marker for SAP.MethodsSAP was induced in rats with an intraperitoneal injection of L-arginine. CD64 expression in the rat pancreas was determined by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry. Additionally, the CD64 mRNA expression in peripheral blood leukocytes from 21 patients with mild acute pancreatitis (MAP) and 10 patients with SAP was investigated at the time of admission and during remission by qRT-PCR.ResultsCD64 mRNA and protein expression in the pancreas was significantly higher in rats with SAP, compared to the controls. The CD64 expression was higher in the patients with SAP than in the patients with MAP. During remission, CD64 mRNA decreased in both the MAP and SAP patients. The area under the curve of CD64 expression for the detection of SAP was superior to both the Ranson and the Acute Physiology and Chronic Health Evaluation II scores.ConclusionsThe CD64 level was significantly increased in correlation with the disease severity in SAP and may act as a useful marker for predicting the development of SAP.

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“…We have previously utilized this technology to investigate intravascular, transendothelial, and extravascular leukocyte migration in the pancreas. 11 In the present study, we evaluated 4D intravital microscopy for study of leukocyte recruitment and migration in HCC tissue in mice.…”

Section: Introductionmentioning

confidence: 99%

4-Dimensional Intravital Microscopy: A New Model for Studies of Leukocyte Recruitment and Migration in Hepatocellular Cancer in Mice

Takeichi

Engelmann

Mocevicius

et al. 2010

Journal of Gastrointestinal Surgery

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Intracapillary leucocyte accumulation as a novel antihaemorrhagic mechanism in acute pancreatitis in mice

Cited by 17 publications

References 52 publications

α_Lβ₂ Integrin is indispensable for CD8⁺ T‐cell recruitment in experimental pancreatic and hepatocellular cancer

α_Lβ₂ Integrin is indispensable for CD8⁺ T‐cell recruitment in experimental pancreatic and hepatocellular cancer

CD64 Expression Is Increased in Patients with Severe Acute Pancreatitis: Clinical Significance

4-Dimensional Intravital Microscopy: A New Model for Studies of Leukocyte Recruitment and Migration in Hepatocellular Cancer in Mice

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Intracapillary leucocyte accumulation as a novel antihaemorrhagic mechanism in acute pancreatitis in mice

Cited by 17 publications

References 52 publications

αLβ2 Integrin is indispensable for CD8+ T‐cell recruitment in experimental pancreatic and hepatocellular cancer

αLβ2 Integrin is indispensable for CD8+ T‐cell recruitment in experimental pancreatic and hepatocellular cancer

CD64 Expression Is Increased in Patients with Severe Acute Pancreatitis: Clinical Significance

4-Dimensional Intravital Microscopy: A New Model for Studies of Leukocyte Recruitment and Migration in Hepatocellular Cancer in Mice

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α_Lβ₂ Integrin is indispensable for CD8⁺ T‐cell recruitment in experimental pancreatic and hepatocellular cancer

α_Lβ₂ Integrin is indispensable for CD8⁺ T‐cell recruitment in experimental pancreatic and hepatocellular cancer