Role of beta-1 integrins on CSF neutrophils in a rabbit model of meningitis

Mark Rowin, Robert Pretzlaff, Vivian Xue, Jose Irazuzta

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Introduction: Integrins are cell surface heterodimers that play a pivotal role in inflammation by allowing PMNs to adhere to the endothelium and migrate through the extracellular matrix. We have previously demonstrated an increased expression of both β1 and β2 integrins on neutrophils in a rabbit with meningitis. We now examine the physiologic role of β1 integrins on neutrophils collected from the CSF in an animal model of meningitis. Methods: The cisterna magnat was punctured on adult New Zealand White rabbits (n = 18) and the subarachnoid space was inoculated with 0.4 ml of a saline solution containing 1 × 102 cfu/ml of group B streptococcus. The rabbits were allowed to recover with free access to food and water. Sixteen hours post-inoculation the rabbits were treated with Ceftriaxone (50 mg/kg). The animals were then anesthetized, placed on maintenance IV fluids and mechanically ventilated for 10 hours. At 28 hours post-inoculation, a cisternal tap was performed and 1 ml of CSF was removed. Neutrophils were recovered from the CSF and using flow cytometry, were analyzed for the expression of the activated β1 integrin isoform. Concurrent analyses of brain (myeloperoxidase) and blood brain barrier (glucose, protein, glucose ratio) injury were performed. Results and Conclusions: The data demonstrate that activated β1 integrin expression on CSF neutrophils have a correlation with injury to both the brain and the blood brain barrier. Using regression analysis, we demonstrated that increased activated β1 integrin activity has a correlation with decreasing CSF glucose (r=0.6, r2 = 0.35, p=0.02) and the serum/CSF glucose ratio (r=0.73, r2 = 0.54, p=0.002). Regression analysis approached significance when CSF protein was compared to activated β1 integrin. The activated β1 integrin isoform also showed a direct correlation to myeloperoxidase activity in brain tissue (r=0.61, r2 = 0.38, p=0.03). These data support a role for β1 integrins on neutrophils in the pathophysiologic consequences of meningitis.

Original languageEnglish (US)
JournalCritical Care Medicine
Volume27
Issue number1 SUPPL.
StatePublished - 1999
Externally publishedYes

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Integrin beta Chains
Meningitis
Integrins
Neutrophils
Rabbits
Blood-Brain Barrier
Glucose
Peroxidase
Protein Isoforms
Regression Analysis
Subarachnoid Space
Streptococcus agalactiae
Macrophage Colony-Stimulating Factor
Ceftriaxone
Wounds and Injuries
Brain
Sodium Chloride
Endothelium
Extracellular Matrix
Flow Cytometry

All Science Journal Classification (ASJC) codes

  • Critical Care and Intensive Care Medicine

Cite this

Role of beta-1 integrins on CSF neutrophils in a rabbit model of meningitis. / Rowin, Mark; Pretzlaff, Robert; Xue, Vivian; Irazuzta, Jose.

In: Critical Care Medicine, Vol. 27, No. 1 SUPPL., 1999.

Research output: Contribution to journalArticle

Rowin, M, Pretzlaff, R, Xue, V & Irazuzta, J 1999, 'Role of beta-1 integrins on CSF neutrophils in a rabbit model of meningitis', Critical Care Medicine, vol. 27, no. 1 SUPPL..
Rowin, Mark ; Pretzlaff, Robert ; Xue, Vivian ; Irazuzta, Jose. / Role of beta-1 integrins on CSF neutrophils in a rabbit model of meningitis. In: Critical Care Medicine. 1999 ; Vol. 27, No. 1 SUPPL.
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abstract = "Introduction: Integrins are cell surface heterodimers that play a pivotal role in inflammation by allowing PMNs to adhere to the endothelium and migrate through the extracellular matrix. We have previously demonstrated an increased expression of both β1 and β2 integrins on neutrophils in a rabbit with meningitis. We now examine the physiologic role of β1 integrins on neutrophils collected from the CSF in an animal model of meningitis. Methods: The cisterna magnat was punctured on adult New Zealand White rabbits (n = 18) and the subarachnoid space was inoculated with 0.4 ml of a saline solution containing 1 × 102 cfu/ml of group B streptococcus. The rabbits were allowed to recover with free access to food and water. Sixteen hours post-inoculation the rabbits were treated with Ceftriaxone (50 mg/kg). The animals were then anesthetized, placed on maintenance IV fluids and mechanically ventilated for 10 hours. At 28 hours post-inoculation, a cisternal tap was performed and 1 ml of CSF was removed. Neutrophils were recovered from the CSF and using flow cytometry, were analyzed for the expression of the activated β1 integrin isoform. Concurrent analyses of brain (myeloperoxidase) and blood brain barrier (glucose, protein, glucose ratio) injury were performed. Results and Conclusions: The data demonstrate that activated β1 integrin expression on CSF neutrophils have a correlation with injury to both the brain and the blood brain barrier. Using regression analysis, we demonstrated that increased activated β1 integrin activity has a correlation with decreasing CSF glucose (r=0.6, r2 = 0.35, p=0.02) and the serum/CSF glucose ratio (r=0.73, r2 = 0.54, p=0.002). Regression analysis approached significance when CSF protein was compared to activated β1 integrin. The activated β1 integrin isoform also showed a direct correlation to myeloperoxidase activity in brain tissue (r=0.61, r2 = 0.38, p=0.03). These data support a role for β1 integrins on neutrophils in the pathophysiologic consequences of meningitis.",
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AB - Introduction: Integrins are cell surface heterodimers that play a pivotal role in inflammation by allowing PMNs to adhere to the endothelium and migrate through the extracellular matrix. We have previously demonstrated an increased expression of both β1 and β2 integrins on neutrophils in a rabbit with meningitis. We now examine the physiologic role of β1 integrins on neutrophils collected from the CSF in an animal model of meningitis. Methods: The cisterna magnat was punctured on adult New Zealand White rabbits (n = 18) and the subarachnoid space was inoculated with 0.4 ml of a saline solution containing 1 × 102 cfu/ml of group B streptococcus. The rabbits were allowed to recover with free access to food and water. Sixteen hours post-inoculation the rabbits were treated with Ceftriaxone (50 mg/kg). The animals were then anesthetized, placed on maintenance IV fluids and mechanically ventilated for 10 hours. At 28 hours post-inoculation, a cisternal tap was performed and 1 ml of CSF was removed. Neutrophils were recovered from the CSF and using flow cytometry, were analyzed for the expression of the activated β1 integrin isoform. Concurrent analyses of brain (myeloperoxidase) and blood brain barrier (glucose, protein, glucose ratio) injury were performed. Results and Conclusions: The data demonstrate that activated β1 integrin expression on CSF neutrophils have a correlation with injury to both the brain and the blood brain barrier. Using regression analysis, we demonstrated that increased activated β1 integrin activity has a correlation with decreasing CSF glucose (r=0.6, r2 = 0.35, p=0.02) and the serum/CSF glucose ratio (r=0.73, r2 = 0.54, p=0.002). Regression analysis approached significance when CSF protein was compared to activated β1 integrin. The activated β1 integrin isoform also showed a direct correlation to myeloperoxidase activity in brain tissue (r=0.61, r2 = 0.38, p=0.03). These data support a role for β1 integrins on neutrophils in the pathophysiologic consequences of meningitis.

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