Elsevier

Surgery

Volume 128, Issue 2, August 2000, Pages 327-331
Surgery

Society of University Surgeons
Endothelial selectin blockade attenuates lung permeability of experimental acid aspiration*,**

Presented at the 61st Annual Meeting of the Society of University Surgeons, Toronto, Ontario, Canada, February 10-12, 2000.
https://doi.org/10.1067/msy.2000.108216Get rights and content

Abstract

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 125I-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-Ig½ 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. (Surgery 2000;128:327-31.)

Section snippets

Description of recombinant proteins

rPSGL-Ig fusion protein (Genetics Institute, Cambridge, Mass) was derived from pED.47.Fc, a recombinant soluble form of PSGL-1 fused to human IgG1.15 Polymerase chain reaction was performed on the Fc portion of this plasmid by using 5′ primer: TAAATAGCGGCCGCACACATGCC-CACCGTGCCCAGCACCTGAAGCCCTGGGGGCACCGTCAGTCTTCCTC and 3′ primer: GCATGTTGCACCGAGGCCCCAGAATCA. The polymerase chain reaction product was digested with the restriction enzymes Not I and Kpn I and ligated to the large fragment of

Results

Acid aspiration in mice (n = 19) led to a marked rise in PI, 0.071 ± 0.008, compared with saline aspirated sham animals (n = 10), PI 0.007 ± 0.001 (P <.05, Fig 1).

. Moderation of acid aspiration induced lung injury by PMN depletion and endothelial selectin blockade. PMN depletion reduced lung PI after acid aspiration by 63% compared with injured untreated group. Mice treated with rPSGL-Ig had a 59% reduction in PI compared with injured untreated animals. Treatment with m20ek.Fc, negative control

Discussion

This study examines the role of PMN-endothelial selectin adhesion mechanisms in mediating acid aspiration lung injury. Neutropenic mice had a 63% reduction in lung injury after acid aspiration. This is similar to previous reports including other animal species.7, 8, 9, 10, 11 Prior work from this laboratory has shown that experimental lavage with leukotriene B4 into the airways of rats induced the synthesis of local tumor necrosis factor–α that in turn led to PMN diapedesis.11 The importance of

Acknowledgements

We thank Mr Gray Shaw of Genetics Institute, Cambridge, Mass, for the generous donation of rPSGL-Ig and m20ek.Fc used in the experiments.

References (23)

  • C Kyriakides et al.

    Membrane attack complex of complement and neutrophils mediate the injury of acid aspiration

    J Appl Physiol

    (1999)
  • Cited by (0)

    *

    Supported in part by the National Institutes of Health grants GM-52585, GM-35141-09, GM-24891-18, The Brigham Surgical Group, Inc; and The Trauma Research Foundation.

    **

    Reprint requests: Herbert B. Hechtman, MD, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115.

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