Aspiration-induced lung injury: Role of complement

R. Rabinovici, L. F. Neville, F. Abdullah, D. R. Phillip, J. Vernick, K. L L Fong -, L. Hillegas, G. Feuerstein

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Objectives: To examine the role of complement in the development of acid aspiration-induced lung injury in the rat. It was postulated that inhibition or depletion of complement attenuates aspiration-induced lung injury. Design: Controlled animal trial. Setting: Animal Laboratory, Jefferson Medical College, Philadelphia, PA. Subjects: Anesthetized rats. Interventions: Aspiration was induced by the intratracheal administration of 0.2 mL of 0.1 N hydrochloric acid (n = 7) and lung injury was evaluated by determining water content, myeloperoxidase activity, protein concentration, and leukocyte count in bronchoalveolar lavage fluid. Muscle PO2 was directly measured using a thin-film chamber oxygen sensor and serum tumor necrosis factor-α was assayed by enzyme-linked immunosorbent assay. The effect of complement inhibition by recombinant human soluble complement receptor type 1 (n = 8) or complement depletion by cobra venom factor (n = 7) on lung injury was evaluated. Measurements and Main Results: Acid aspiration induced pulmonary leukosequestration, edema, and a microvascular permeability defect, along with tissue hypoxia. Pretreatment with soluble complement receptor type 1 (complement inhibition) or cobra venom factor (complement depletion) significantly reduced lung edema (-61 ± 7% ;p <.05), eliminated protein accumulation in bronchoalveolar lavage fluid (p <.01), and improved (p <.05) tissue oxygenation. In contrast, there was no effect of soluble complement receptor type 1 or of cobra venom factor on leukosequestration. Conclusions: Acid aspiration induces lung injury through a complement- dependent mechanism that leads to microvascular permeability defects. Therefore, the possibility that complement inhibitors may have a salutary effect in humans with aspiration-induced lung injury should be investigated.

Original languageEnglish (US)
Pages (from-to)1405-1411
Number of pages7
JournalCritical Care Medicine
Volume23
Issue number8
DOIs
StatePublished - 1995
Externally publishedYes

Keywords

  • adult respiratory distress syndrome
  • complement factors
  • complement receptor
  • critical illness
  • cytokines
  • leukocytes
  • lung
  • lung injury
  • oxygen
  • pneumonia aspiration
  • pulmonary emergencies

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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