Monocytes and lymphocytes as active participants in the pathogenesis of experimental shock.
We investigated the role played by monocytes and lymphocytes in the pathogenesis of experimental shock. Splanchnic artery occlusion (SAO) shock was induced in anaesthetized rats by clamping splanchnic arteries for 45 min followed by reperfusion. Sham operated animals were used as controls. SAO shocked rats had a decreased survival time (80 +/- 11 min, while sham shocked rats survived more than 4 h), increased serum (248 +/- 21 U/ml) and macrophage (145 +/- 15 U/ml) levels of TNF-alpha, enhanced myeloperoxidase (MPO) activity in the ileum (3.38 +/- 0.2 U x 10(-3)/g tissue), decreased number of monocytes, lymphocytes and neutrophils and a profound hypotension. In addition we found an increased expression of vascular cell adhesion molecule-1 (VCAM-1) on aortic endothelium and a reduced percentage of VLA-4 positive monocytes and lymphocytes. Inhibition of TNF-alpha synthesis, reversed the increased endothelial expression of VCAM-1, increased the percentage of integrin VLA-4 positive leukocytes and improved monocyte, lymphocyte and neutrophil count. Furthermore a passive immunization with specific antibodies raised against VCAM-1 (2 mg/kg, i.v. 3 h before SAO) increased survival, reduced MPO activity in the ileum (0.034 +/- 0.04 U x 10(-3)/g tissue) and improved mean arterial blood pressure. Our data suggest that monocytes and lymphocytes participate in the pathogenesis of splanchnic ischaemia-reperfusion injury and may amplify the adhesion of neutrophils to peripheral tissues.
Altavilla
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Institute of Pharmacology, School of Medicine, University of Messina, Italy.
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Canale
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Ioculano
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Musolino
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Alonci
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Sardella
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AP
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D004730:Endothelium, Vascular / Q000473:pathology / Q000502:physiology; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007422:Intestines / Q000098:blood supply / Q000473:pathology* / Q000503:physiopathology; D007511:Ischemia / Q000473:pathology* / Q000503:physiopathology; D007958:Leukocyte Count; D008214:Lymphocytes / Q000502:physiology*; D008297:Male; D009000:Monocytes / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000502:physiology; D015427:Reperfusion Injury / Q000473:pathology* / Q000503:physiopathology; D012769:Shock / Q000473:pathology* / Q000503:physiopathology; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D009195:Peroxidase