Inhibition of CD18 or CD11b attenuates acute lung injury after acid instillation in rabbits

Journal of Applied Physiology
H G Folkesson, M A Matthay

Abstract

Acid-induced lung injury is mediated primarily by activated neutrophils. Although a prior study demonstrated that acid-induced neutrophil influx into the air spaces was not CD18 dependent, we hypothesized that either a neutralizing anti-CD18 monoclonal antibody (MHM23) or a neutrophil inhibitory factor (NIF), NIF (CD11b,18), might attenuate acid-induced lung injury in rabbits by interfering with neutrophil activation. This hypothesis derived from in vitro stu ies that reported that anti-CD18 therapy prevented tumor necrosis factor-alpha-induced neutrophil activation. Hydrochloric acid (pH = 1.5 in one-third normal saline) or one-third normal saline (4 ml/kg) was instilled into the lungs of ventilated, anesthetized rabbits. The rabbits were studied for 6 h. In acid-instilled rabbits without the anti-CD18 monoclonal antibody or NIF (CD11b,18), severe lung injury developed. In acid-instilled rabbits, pretreatment (5 min before acid) with the anti-CD18 monoclonal antibody (2 mg/kg i.v.) or pretreatment with the NIF (anti-CD11b,18, 10 mg/kg i.v.) prevented 50-70% of acid-induced abnormalities in oxygenation, the increase in extravascular lung water, and extravascular protein accumulation. The anti-CD18 monoclonal antibody was associ...Continue Reading

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Citations

Apr 27, 2000·American Journal of Physiology. Lung Cellular and Molecular Physiology·C M WoodsS F Flaim
Mar 15, 2006·Current Opinion in Anaesthesiology·Karen BosmaV Marco Ranieri
Feb 12, 2008·American Journal of Physiology. Lung Cellular and Molecular Physiology·Danielle Morse, Augustine M K Choi
Jun 24, 2003·American Journal of Physiology. Lung Cellular and Molecular Physiology·Evan S OngAsrar B Malik
Sep 1, 2005·Anesthesiology·Beatrice Beck-SchimmerRalph C Schimmer
Aug 3, 2011·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Kaushik Parthasarathi, Jahar Bhattacharya
May 9, 2012·American Journal of Physiology. Lung Cellular and Molecular Physiology·Kaushik Parthasarathi
Oct 29, 2000·American Journal of Physiology. Lung Cellular and Molecular Physiology·M A MoxleyJ A Corbett
Jun 5, 2012·American Journal of Physiology. Lung Cellular and Molecular Physiology·Hans G FolkessonMark A Simmons
Nov 11, 2020·British Journal of Pharmacology·Alireza TahamtanVahid Salimi
Sep 24, 1999·The American Journal of Medicine·R Paine, P A Ward

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