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Endothelial selectin blockade attenuates lung permeability of experimental acid aspiration
C Kyriakides1, W Austen, Y Wang
1Department of Surgery, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA.
Background:
A central role for the polymorphonuclear leukocyte (PMN) in experimental acid aspiration has been demonstrated by the observation that PMN depletion reduced pulmonary vascular permeability. This study investigates the role of recombinant soluble P-selectin glycoprotein ligand-immunoglobulin fusion protein (rPSGL-Ig), a P- and E-selectin antagonist in moderating acid aspiration lung injury.
Methods:
Tracheostomy tubes were placed in male C57BL/6 mice and 0.1 N HCl was instilled into the trachea at 2 mL/kg after intravenous injection of (125)I-albumin. After 4 hours the lung vascular permeability index (PI) and PMN accumulation in the bronchoalveolar lavage fluid were assessed.
Results:
PI in neutropenic mice was 63% reduced compared with the untreated group and similar to the PI of mice treated with 1 mg/kg rPSGL-Ig before acid aspiration. PMN count of 19 +/- 5 in the bronchoalveolar lavage fluid in rPSGL-Ig treated mice was significantly less than the untreated group PMN count of 586 +/- 72. The respective PI in mice treated with rPSGL-Ig (1/2) hour and 1 hour after acid aspiration was 45% and 39% reduced compared with the untreated group.
Conclusions:
Endothelial selectin blockade is as effective as PMN depletion in moderating acid aspiration induced lung permeability. Delayed antiselectin therapy can decrease lung injury.
Insights
Blocking selectins with rPSGL-Ig significantly reduces lung injury from acid aspiration, similar to polymorphonuclear leukocyte (PMN) depletion. Delayed treatment also effectively decreases lung permeability and PMN accumulation.
Area of Science:
- Pulmonary Medicine
- Immunology
- Inflammation Research
Background:
- Polymorphonuclear leukocytes (PMNs) play a key role in experimental acid aspiration lung injury.
- PMN depletion has been shown to reduce pulmonary vascular permeability in these models.
Purpose of the Study:
- To investigate the efficacy of recombinant soluble P-selectin glycoprotein ligand-immunoglobulin fusion protein (rPSGL-Ig) as a P- and E-selectin antagonist.
- To determine if rPSGL-Ig can moderate acid aspiration-induced lung injury.
Main Methods:
- Male C57BL/6 mice underwent tracheostomy and received 0.1 N HCl (2 mL/kg) via trachea after intravenous (125)I-albumin injection.
- Lung vascular permeability index (PI) and PMN accumulation in bronchoalveolar lavage fluid were assessed after 4 hours.
Main Results:
- rPSGL-Ig treatment reduced PI by 63%, comparable to PMN depletion.
- PMN counts in bronchoalveolar lavage fluid were significantly lower in rPSGL-Ig treated mice (19 +/- 5) versus untreated controls (586 +/- 72).
- Delayed rPSGL-Ig administration (0.5-1 hour post-aspiration) reduced PI by 45% and 39%.
Conclusions:
- Endothelial selectin blockade is as effective as PMN depletion in mitigating acid aspiration-induced lung permeability.
- Antiselectin therapy, even when delayed, demonstrates potential in reducing lung injury.