|Antibody to E- and L-selectin does not prevent lung injury or mortality in septic baboons.|
|PMID: 9517615 Owner: NLM Status: MEDLINE|
|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.|
|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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|Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.|
|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|
|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|
|Languages: eng Pagination: 938-49 Citation Subset: AIM; IM|
|Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.|
|APA/MLA Format Download EndNote Download BibTex|
Antibodies, Monoclonal / administration & dosage, therapeutic use*
Carbon Dioxide / blood
Cell Adhesion Molecules / immunology
Chemotaxis, Leukocyte / immunology
E-Selectin / immunology*
Escherichia coli Infections / complications*
Hypertension, Pulmonary / microbiology
Hypotension / microbiology
L-Selectin / immunology*
Neutrophils / immunology
Oxygen / blood
Pulmonary Gas Exchange
Respiratory Distress Syndrome, Adult / microbiology, prevention & control*
Sepsis / complications*
|5PO1 HL42444-07/HL/NHLBI NIH HHS|
|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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