Pulmonary vascular sequestration of neutrophils in endotoxemia is initiated by an effect of endotoxin on the neutrophil in the rabbit
Endotoxemia causes neutrophil sequestration in the pulmonary vascular bed. Such sequestration may be a critical initiating event in the generation of microvascular injury, although the mechanisms that lead to this localization are not understood. To investigate these phenomena, the following study employed intravenous pulses of /sup 111/Indium-tropolonate-labeled neutrophils (/sup 111/In-neutrophils), which circulated in the rabbit with normal kinetics and responded in a manner indistinguishable from unlabeled, circulating neutrophils in response to an intravenous injection of purified endotoxic lipopolysaccharide (LPS) or epinephrine. Pulmonary sequestration of /sup 111/In-neutrophils was assessed by quantitative external gamma camera scintigraphy of a lung suprahilar region of interest. Noninvasive assessment of radioactivity by this method accurately reflected total lung radioactivity, which was shown by autoradiography to be confined to the injected /sup 111/In-neutrophils. Intravenously administered LPS caused a marked, dose-dependent sequestration of /sup 111/In-neutrophils in the pulmonary vasculature, and exhaustive ultrastructural autoradiography showed discretely radiolabeled neutrophils located within pulmonary capillaries. A distinct effect was seen with an intravenous injection of as little as 100 ng per rabbit (i.e., 500 pg/ml blood). A 5-min ex vivo pretreatment of /sup 111/In-neutrophils with 10 ng to 10 micrograms/ml LPS in heat-inactivated plasma also caused dose-dependent pulmonary sequestration of the pretreated /sup 111/In-neutrophils but did not cause generalized neutropenia in recipient rabbits.
- Research Organization:
- National Jewish Center for Immunology and Respiratory Medicine, Denver, CO
- OSTI ID:
- 6277216
- Journal Information:
- Am. Rev. Respir. Dis.; (United States), Vol. 136:1
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
ENDOTOXINS
BIOLOGICAL EFFECTS
HEMIC DISEASES
PATHOGENESIS
LUNGS
SCINTISCANNING
NEUTROPHILS
REMOVAL
AUTORADIOGRAPHY
DOSE-RESPONSE RELATIONSHIPS
INDIUM 111
INTRAVENOUS INJECTION
LIPOPOLYSACCHARIDES
RABBITS
ANIMALS
ANTIGENS
BETA DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CARBOHYDRATES
COUNTING TECHNIQUES
DAYS LIVING RADIOISOTOPES
DIAGNOSTIC TECHNIQUES
DISEASES
ELECTRON CAPTURE RADIOISOTOPES
INDIUM ISOTOPES
INJECTION
INTAKE
INTERMEDIATE MASS NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
LEUKOCYTES
LIPIDS
MAMMALS
MATERIALS
MINUTES LIVING RADIOISOTOPES
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
POLYSACCHARIDES
RADIOISOTOPE SCANNING
RADIOISOTOPES
RESPIRATORY SYSTEM
SACCHARIDES
TOXIC MATERIALS
TOXINS
VERTEBRATES
550601* - Medicine- Unsealed Radionuclides in Diagnostics
550901 - Pathology- Tracer Techniques