Attenuation of tumor necrosis factor-induced endothelial cell cytotoxicity and neutrophil chemiluminescence

Journal Article · Thu Nov 01 04:00:00 EST 1990 · American Review of Respiratory Disease (New York); (USA)

DOI:https://doi.org/10.1164/ajrccm/142.5.1073· OSTI ID:6272085

Zheng, H; Crowley, J J; Chan, J C; Hoffmann, H; Hatherill, J R; Ishizaka, A; Raffin, T A ^[1]

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1. Stanford Univ. Medical Center, CA (USA)

Our laboratory has previously shown that the administration of tumor necrosis factor (TNF), a cytokine produced by activated mononuclear cells, to guinea pigs produces a syndrome similar to gram-negative sepsis or ARDS. Pentoxifylline (PTX), a methylxanthine, protects against TNF-induced and sepsis-induced acute lung injury in vivo. We now report on in vitro cellular studies of PMN-mediated cellular injury and its attenuation. We studied TNF-induced bovine pulmonary artery endothelial cell (EC) cytotoxicity both with and without PMN. A 51Cr release assay was used to measure EC damage. Further, we investigated PMN function in response to TNF by measuring chemiluminescence. Agents that attenuate EC damage and PMN activation were evaluated in the above assays. Results revealed that TNF causes EC injury (p less than 0.05) and PMN increase TNF-induced EC injury. Furthermore, PTX, aminophylline (AMPH), caffeine, and forskolin attenuate TNF-induced EC cytotoxicity only in the presence of PMN (p less than 0.05). Of interest, dibutyryl cAMP (DBcAMP) protects EC from TNF-induced injury both with and without PMN. Agents that may increase cAMP levels in PMN (PTX, DBcAMP, forskolin, isobutyl methylxanthine, and terbutaline) significantly attenuate TNF-induced PMN chemiluminescence (p less than 0.05). We conclude that TNF causes EC damage and PMN increase this damage. Furthermore, PTX, AMPH, caffeine, and forskolin can attenuate TNF-induced EC injury in the presence of PMN, whereas DBcAMP attenuates TNF-induced EC injury with and without PMN. In addition, agents that may increase intracellular cAMP levels in PMN can attenuate TNF-induced PMN chemiluminescence. Thus, these agents likely attenuate TNF-induced PMN-mediated EC injury through their inhibitory effects on PMN.

• OSTI ID: 6272085
• Journal Information: American Review of Respiratory Disease (New York); (USA), Journal Name: American Review of Respiratory Disease (New York); (USA) Vol. 142:5; ISSN ARDSB; ISSN 0003-0805
• Country of Publication: United States
• Language: English

Related Subjects

550901* -- Pathology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMP
ANALEPTICS
ANIMAL TISSUES
ANIMALS
AROMATICS
ARTERIES
AZAARENES
BETA DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BIOLOGICAL FUNCTIONS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BLOOD VESSELS
BODY
BODY FLUIDS
CAFFEINE
CARDIOVASCULAR SYSTEM
CATTLE
CENTRAL NERVOUS SYSTEM AGENTS
CHEMILUMINESCENCE
CHROMIUM 51
CHROMIUM ISOTOPES
DOMESTIC ANIMALS
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ENDOTHELIUM
EVEN-ODD NUCLEI
FUNCTIONS
HETEROCYCLIC COMPOUNDS
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
LEUKOCYTES
LUMINESCENCE
LUNGS
MAMMALS
MATERIALS
NEUTROPHILS
NUCLEI
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
PATHOLOGICAL CHANGES
PROTEINS
PURINES
RADIOASSAY
RADIOISOTOPES
RESPIRATORY SYSTEM
RUMINANTS
TISSUES
TRACER TECHNIQUES
VERTEBRATES
XANTHINES