Granulocyte Colony-Stimulating Factor Inhibits Neutrophil Apoptosis at the Local Site after Severe Head and Thoracic Injury
| Autor: | Hans Georg Imhof, Otmar Trentz, Wolfgang Ertel, Marius Keel, Thomas Hartung, Ulrich Buergi |
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| Rok vydání: | 1999 |
| Předmět: |
Adult
Pathology medicine.medical_specialty Adolescent Thoracic Injuries Neutrophils Apoptosis Granulocyte chemistry.chemical_compound Cerebrospinal fluid Granulocyte macrophage colony-stimulating factor receptor Granulocyte Colony-Stimulating Factor medicine Craniocerebral Trauma Humans Glasgow Coma Scale Propidium iodide Cells Cultured Aged Cerebrospinal Fluid Respiratory Burst medicine.diagnostic_test Multiple Trauma business.industry Hydrogen Peroxide Middle Aged Respiratory burst Granulocyte colony-stimulating factor N-Formylmethionine Leucyl-Phenylalanine Orthopedics Bronchoalveolar lavage medicine.anatomical_structure chemistry Abbreviated Injury Scale Cytokines business Bronchoalveolar Lavage Fluid |
| Zdroj: | The Journal of Trauma: Injury, Infection, and Critical Care. 46:784-793 |
| ISSN: | 1079-6061 |
| Popis: | BACKGROUND Tissue injury from mechanical trauma often leads to secondary organ failure. Local accumulation of neutrophils and excessive release of toxic metabolites through inhibition of neutrophil apoptosis may be responsible for capillary leakage and irreversible damage of resident cells of injured tissues. METHODS The purpose of this study was to examine the presence of apoptosis-inhibiting factors at the local site of tissue injury. Cerebrospinal fluid (CSF) from patients with severe head injury (n = 10; Abbreviated Injury Scale score, 4.5 +/- 0.2 points) and bronchoalveolar lavage fluid (BALF) from patients with serious chest trauma (n = 10; Abbreviated Injury Scale score, 4.1 +/- 0.1 points) were collected on days 1 and 3 after injury and compared with CSF (n = 5) and BALF (n = 16) obtained from patients undergoing elective orthopedic surgery. Neutrophils from healthy humans were incubated with 10% of CSF or BALF for 16 hours. Neutrophil apoptosis was determined by flow cytometric analysis of propidium iodide nuclear staining, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling, and May-Grunwald-Giemsa staining. Levels of granulocyte colony-stimulating factor (G-CSF) in CSF and BALF were measured with enzyme-linked immunosorbent assay. RESULTS CSF and BALF from injured patients significantly inhibited spontaneous neutrophil apoptosis of healthy humans compared with control samples, whereas respiratory burst activity was enhanced (p < 0.05). Moreover, CSF and BALF from injured patients contained increased (p < 0.05) amounts of G-CSF. Neutralization of G-CSF in CSF and BALF from injured patients using monoclonal anti-G-CSF antibody markedly (p < 0.05) reduced the apoptosis-inhibiting effect of those body fluids and decreased the respiratory burst. CONCLUSION In patients with severe head or chest injury, G-CSF acts locally as a strong inhibitor of spontaneous neutrophil apoptosis, which may cause an increased destructive potential of neutrophils present in injured tissues. |
| Databáze: | OpenAIRE |
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