Intratracheal administration of endotoxin and cytokines: VIII. LPS induces E-selectin expression; anti-E-selectin and soluble E-selectin inhibit acute inflammation.
E-selectin is an inducible endothelial adhesion molecule that binds neutrophils. E-selectin mRNA is not constitutively detectable in the lungs of rats. Intratracheal injection of LPS induces pulmonary E-selectin mRNA expression at 2-4 h. Intratracheal injection of LPS followed at 2 and 4 h by intravenous injection of mouse F(ab')2 or F(ab') anti-E-selectin monoclonal antibody inhibits the emigration of neutrophils into the bronchoalveolar space at 6 h by 50-70%. TNF and IL-6 bioactivity are not decreased in bronchoalveolar lavage fluid after treatment with anti-E-selectin antibody as compared to controls, suggesting that the anti-E-selectin does not affect the magnitude of the LPS-initiated cytokine cascade. Intratracheal injection of LPS followed at 2 and 4 h by intravenous injection of soluble E-selectin inhibits neutrophilic emigration at 6 h by 64%, suggesting that endogenous soluble E-selectin shed from activated endothelium may play a role in the endogenous down-regulation of acute inflammation. E-selectin-mediated adhesion of neutrophils to endothelium appears crucial to the full development of the acute inflammation response.
Ulich
T R
TR
Department of Pathology, UC San Diego School of Medicine 92103.
Howard
S C
SC
Remick
D G
DG
Yi
E S
ES
Collins
T
T
Guo
K
K
Yin
S
S
Keene
J L
JL
Schmuke
J J
JJ
Steininger
C N
CN
D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000917:Antibody Formation; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000276:immunology* / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology*; D019040:E-Selectin; D004731:Endotoxins / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007267:Injections; D007275:Injections, Intravenous; D007375:Interleukin-1; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D011014:Pneumonia / Q000139:chemically induced / Q000517:prevention & control*; D051381:Rats; D011917:Rats, Inbred Lew; D012995:Solubility; D014132:Trachea
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D016207:Cytokines; D019040:E-Selectin; D004731:Endotoxins; D007140:Immunoglobulin Fab Fragments; D007375:Interleukin-1; D008070:Lipopolysaccharides