Human aortic endothelial cells express the type I but not the type II receptor for interleukin-1 (IL-1).
Endothelial cells (EC) are very responsive to the proinflammatory cytokine interleukin-1 (IL-1). EC are induced by IL-1 to secrete chemotactic factors and to increase expression of cell surface adhesion molecules leading to increased leukocyte adhesion. Activated EC further contribute to the inflammatory response by secreting additional cytokines. IL-1 interacts with EC through high-affinity cell-surface receptors. However, the low number of receptors present on EC has made characterization difficult. Further, recent evidence has suggested diversity in the responses of EC from different regions of the vascular system. Interested in the effect of IL-1 on early atherosclerotic lesion formation, we have characterized the IL-1 receptors on human aortic endothelial cells (HAEC). Using a direct binding assay, we found that HAEC have 1,000-3,000 IL-1 receptors per cell and bind IL-1 alpha with a Kd of 3.5 x 10(-10) M. We found that a monoclonal antibody specific for the type I receptor completely blocks IL-1 alpha binding. The blocking antibody also completely inhibits the IL-1 induced increase in intracellular adhesion molecule 1 (ICAM-1) expression by HAEC. Using solution hybridization and ribonuclease protection with an antisense probe, a sensitive method for detection of low abundance mRNA species we found that HAEC as well as human umbilical vein EC (HUVEC) have significant levels of mRNA for the type I IL-1 receptor. To test whether HAEC might also contain transcripts for the type II IL-1 receptor, we compared levels of mRNAs by polymerase chain reaction (PCR) amplification of cDNAs reverse-transcribed from total RNA. We found only transcripts for the type I receptor and not the type II receptor in HAEC. Based on this data, we conclude that aortic endothelial cells respond to IL-1 through the type I receptor.
Marion Merrell Dow Research Institute, Cincinnati, Ohio 45215.
A L
AL
Akeson
L B
LB
Mosher
C W
CW
Woods
K K
KK
Schroeder
T L
TL
Bowlin
D001011:Aorta / Q000166:cytology / Q000378:metabolism*; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007375:Interleukin-1 / Q000378:metabolism; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000145:classification / Q000378:metabolism* / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000235:genetics
D015815:Cell Adhesion Molecules; D007375:Interleukin-1; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D015375:Receptors, Interleukin-2; D018799:Intercellular Adhesion Molecule-1