Interleukin-1beta induces tissue- and cell type-specific expression of adhesion molecules in vivo.
We examined the tissue distribution of adhesion molecule gene expression in mice treated intravenously with interleukin (IL)-1 beta. E-selectin mRNA expression was selectively induced in the heart by IL-1 beta, but only slight or no induction was observed in other organs. On the other hand, intercellular adhesion molecule-1 mRNA expression was inducible in all organs examined, although it showed the strongest induction in the lung and the weakest responses in the brain and skin. Vascular cell adhesion molecule-1 mRNA was also inducible in all organs with the exception of the skin, but it was induced most markedly in the lung and the heart. The accessibility of IL-1 beta to the heart was less than that to other organs except the brain. Similar tissue-specific induction of these mRNAs was also seen when tumor necrosis factor (TNF)-alpha or lipopolysaccharide was substituted for IL-1 beta. Analysis of E-selectin mRNA expression in the heart by in situ hybridization indicated that expression was most prominent in microvascular endothelial cells and some other stromal cells, but this transcript was not seen in the lung. Although intercellular adhesion molecule-1 mRNA expression was restricted to the endothelium lining the capillaries and small arteries in the heart, its distribution in the lung covered not only the endothelium but also the cells composing the alveolar septa. In contrast, vascular cell adhesion molecule-1 mRNA expression was most prominent in endothelial cells of larger vessels in both the heart and the lung. Our results demonstrate that expression of adhesion molecules is tissue- and cell type-specific and that endothelial cells differentially express adhesion molecules depending on the size of the blood vessels.
Pharmaceutical Frontier Research Laboratories, J.T. Central Pharmaceutical Research Institute, Yokohama, Japan.
M
M
Tamaru
K
K
Tomura
S
S
Sakamoto
K
K
Tezuka
T
T
Tamatani
S
S
Narumi
D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D015815:Cell Adhesion Molecules / Q000187:drug effects* / Q000235:genetics; D015342:DNA Probes; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D007150:Immunohistochemistry; D017403:In Situ Hybridization / Q000379:methods; D007375:Interleukin-1 / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009693:Nucleic Acid Hybridization / Q000379:methods; D015345:Oligonucleotide Probes; D009928:Organ Specificity / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D013047:Specific Pathogen-Free Organisms; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D015342:DNA Probes; D007375:Interleukin-1; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha