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January 1997
Intercellular adhesion molecule-1 Mediates Acid Aspiration-induced Lung Injury.
Nagase T, Ohga E, Sudo E, Katayama H, Uejima Y, Matsuse T, Fukauchi Y. Am J Respir Crit Care Med 1996: 154:504-10.
[ see abstract below ]
A clinical problem constantly in the minds of thoughtful anesthesia and
critical care medicine practitioners is that associated with Mendelson's
Syndrome, commonly known as acid aspiration-induced lung injury.
This
phenomenon is considered one of the primary causes of adult respiratory
distress syndrome, ARDS, which carries a high mortality rate (approx 50%).
Although the cause was long considered a result of direct injury of the lung
by acid, this no longer considered the actual injury process. The acid
itself is soon neutralized, and is followed by a series of biological events
beginning with the release of pro-inflammatory mediators, including tissue
necrosing factor, TNF, and interleukin-8, which in turn activate neutrophils
which can produce profound tissue damage.
The process of activation,
recruitment and adhesion of neutrophils to the endothelial lining of
pulmonary blood vessels is mediated first by members of the selectin family
of adhesion molecules, and another immunoglobulin gene/receptor family known
as integrins.
Members of these families involved in the important process
of neutrophil adhesion include a variety of endogenous substances having
names with abbreviations unfamiliar to most clinicians: E-, L- and P
selectins; Beta2 integrins LFA-1 and Mac-1; and intracellular adhesion
molecules (ICAM-1). A very active and extensive approach to therapy for the
treatment of acid aspiration induced lung injury is based on strategies
targeted at these various mediators in the hope that by modifying their
availability the injury process can be minimized. None to date have proven
to be particularly effective in the clinical setting, despite a variety of
creative approaches taken thus far.
This article and some related
information presented in the accompanying editorial demonstrates some
impressive laboratory results in which antibody to ICAM-1, when administered
intratracheally can prevent and treat acid aspiration-induced lung injury in
rats, including the accumulation of neutrophils in the lung with significant
improvements in pulmonary edema, gas exchange, mechanical properties and
histologic indices of lung injury.
Antagonism of both ICAM-1 and
LFA-1alpha produced even greater results than ICAM-1 alone. Although much
more needs to be done before therapy based on this approach will be
routinely available for treating acid aspiration-induced lung injury in
patients, it is well worth watching this rapidly evolving field of
biological research for meaningful answers to this serious clinical problem.
Anesthesiologists and intensivists will likely be among the first to apply
this new knowledge to the treatment and prevention of ARDS.
Return to the Current Literature Review Front Page, or read the abstract:
ABSTRACT
Acid-aspiration-induced injury is one of the leading causes of adult respiratory distress syndrome. Intercellular adhesion molecule-1 (ICAM-1) is a ligand for lymphocyte-function-associated antigen-1 alpha (LFA-1 alpha), and it has been shown to be required for leukocyte migration into inflamed areas.
The purpose of this report was to investigate the role of the ICAM-1/LFA-1 alpha pathway in a rat model of acid-spiration-induced injury. Animals received 3.0 ml/kg HCI (0.1N; pH, 1.0) intratracheally retreated with control monoclonal antibodies (mAbs) (HCI group) or anti-ICAM-1 and LFA-1 alpha mAbs (Test group). In the HCI group, increases in lung resistance (RL) (229 +/- 23% baseline), lung wet-to-dry weight ratio (W/D) (11.9 +/- 0.4), protein concentration (TP) (0.447 +/- 0.054 mg/ml), and the number of neutrophils (PMN) (159.0 +/- 19.4 x 10(4)) of bronchoalveolar lavage fluid were observed.
In the Test group, HCI-induced injury was significantly reduced (RL, 122 +/- 7% baseline; W/D, 7.2 +/- 0.1; TP, 0.277 +/- 0.016 mg/ml; PMN, 8.8 +/- 0.8 x 10(4)). The administration of mAbs to ICAM-1 and LFA-1 alpha after HCI instillation partially attenuated HCI-induced responses. These observations suggest that the ICAM-1/LFA-1 alpha pathway might be involved in the pathogenesis of adult respiratory distress syndrome caused by acid aspiration.
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