Document Detail


Antibody to E- and L-selectin does not prevent lung injury or mortality in septic baboons.
MedLine Citation:
PMID:  9517615     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recruitment of polymorphonuclear leukocytes (PMN) through upregulation of cellular adhesion molecules is a proposed mechanism of injury in sepsis and acute respiratory distress syndrome (ARDS). We hypothesized that pretreatment of baboons with a monoclonal antibody to human E- and L-selectin (EL-246) during sepsis would decrease PMN influx into tissues and result in less organ injury during gram-negative sepsis. We studied 14 anesthetized, ventilated adult baboons; six animals received 1 mg/kg of EL-246 before infusion of an LD100 of live Escherichia coli and six received the E. coli infusion without antibody therapy. Two other animals received 1 mg/kg of EL-246 intravenously without an infusion of bacteria. Intermittent measurements were made of circulatory pressures, cardiac output, urine output, arterial blood gases, ventilation:perfusion ratio (VA/Q), and hematologic status. The experiments were ended at 48 h or at the time of death. Tissues were harvested for pathology and biochemical measurements. The E. coli infusions were associated with a hyperdynamic state, pulmonary hypertension, systemic hypotension, decreased urine output (UOP), and metabolic acidosis. The antibody partly blocked PMN migration, but there were few significant physiologic or biochemical differences between the EL-246-treated and untreated animals. In the antibody-treated animals, UOP was decreased, metabolic acidosis was worsened, and median survival time was decreased significantly. We conclude that treatment with an antibody to E- and L-selectin in gram-negative sepsis does not improve gas exchange or protect against lung injury, and is associated with decreased survival time in primates.
Authors:
M S Carraway; K E Welty-Wolf; S P Kantrow; Y C Huang; S G Simonson; L G Que; T K Kishimoto; C A Piantadosi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  American journal of respiratory and critical care medicine     Volume:  157     ISSN:  1073-449X     ISO Abbreviation:  Am. J. Respir. Crit. Care Med.     Publication Date:  1998 Mar 
Date Detail:
Created Date:  1998-04-07     Completed Date:  1998-04-07     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  938-49     Citation Subset:  AIM; IM    
Affiliation:
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.
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MeSH Terms
Descriptor/Qualifier:
Acidosis / microbiology
Animals
Antibodies, Monoclonal / administration & dosage,  therapeutic use*
Blood Pressure
Carbon Dioxide / blood
Cardiac Output
Cell Adhesion Molecules / immunology
Chemotaxis, Leukocyte / immunology
E-Selectin / immunology*
Escherichia coli Infections / complications*
Humans
Hypertension, Pulmonary / microbiology
Hypotension / microbiology
Injections, Intravenous
L-Selectin / immunology*
Male
Neutrophil Activation
Neutrophils / immunology
Oxygen / blood
Papio
Pulmonary Gas Exchange
Respiration, Artificial
Respiratory Distress Syndrome, Adult / microbiology,  prevention & control*
Sepsis / complications*
Survival Rate
Up-Regulation
Urine
Ventilation-Perfusion Ratio
Grant Support
ID/Acronym/Agency:
5PO1 HL42444-07/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Cell Adhesion Molecules; 0/E-Selectin; 124-38-9/Carbon Dioxide; 126880-86-2/L-Selectin; 7782-44-7/Oxygen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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