Aspiration-induced lung injury: role of complement.

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-alpha 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.

• Authors: R Rabinovici, L F Neville, F Abdullah, D R Phillip, J Vernick, K L Fong, L Hillegas, G Feuerstein
• Journal: Critical care medicine (Crit Care Med) Vol. 23 Issue 8 Pg. 1405-11 (Aug 1995) ISSN: 0090-3493 [Print] United States
• PMID: 7634812 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Elapid Venoms
• Receptors, Complement
• Recombinant Proteins
• cobra venom factor
• soluble complement inhibitor 1
• Complement System Proteins
• Hydrochloric Acid

Topics

• Animals
• Capillary Permeability
• Complement Activation (drug effects)
• Complement System Proteins (physiology)
• Disease Models, Animal
• Elapid Venoms (pharmacology)
• Enzyme-Linked Immunosorbent Assay
• Hydrochloric Acid
• Male
• Pneumonia, Aspiration (chemically induced, drug therapy, immunology)
• Premedication
• Rats
• Rats, Sprague-Dawley
• Receptors, Complement (physiology)
• Recombinant Proteins