Beta 2-integrin-mediated signal up-regulates counterreceptor ICAM-1 expression on human monocytic cell line THP-1 through tyrosine phosphorylation.
Intracellular cross-talk between LFA-1 and its counter receptor, intercellular adhesion molecule-1 (ICAM-1), on human monocytic cell line THP-1 was analyzed. Stimulation with mAb YH384 specific for LFA-1 alpha (CD11a) up-regulated ICAM-1 expression on THP-1 cells. Cell surface expression of ICAM-1 on THP-1 cells was dose-dependently up-regulated and reached the maximal level 24 hr after stimulation with mAb YH384. Up-regulation of ICAM-1 by mAb YH384 was further confirmed by Northern blotting analysis at the mRNA level, and the maximal message of ICAM-1 was observed 4 hr after stimulation. mAb YH384-induced upregulation of cell surface expression was ICAM-1-specific, and the expression of the other nine molecules tested was not augmented. Up-regulation of ICAM-1 was also observed following stimulation with other mAb specific for CD11a (S6F1), CD11b (JML-H11), and CD18 (IB4); all of these mAb recognized members of the beta 2-integrin family, but not with isotype-matched control mAb. The mAb 4B4 (specific for beta 1-integrin) similarly, but more weakly, augmented ICAM-1 expression. The effect of mAb YH384 on expression of ICAM-1 was dose-dependently suppressed by treatment with herbimycin A or genistein, both inhibitors of tyrosine kinase. These results suggest that beta 2-integrin-mediated up-regulation of ICAM-1 is mediated via a tyrosine phosphorylation pathway.
Yamada
A
A
Department of Immunology, Kurume University School of Medicine, Japan.
Hara
A
A
Inoue
M
M
Kamizono
S
S
Higuchi
T
T
Itoh
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D016227:Benzoquinones; D018821:CD18 Antigens / Q000502:physiology*; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015973:Gene Expression Regulation, Leukemic; D019833:Genistein; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D007529:Isoflavones / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D007948:Leukemia, Monocytic, Acute / Q000473:pathology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000276:immunology*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D016227:Benzoquinones; D018821:CD18 Antigens; D004791:Enzyme Inhibitors; D007529:Isoflavones; D047029:Lactams, Macrocyclic; D016169:Lymphocyte Function-Associated Antigen-1; D009363:Neoplasm Proteins; D011809:Quinones; D018799:Intercellular Adhesion Molecule-1; D017828:Rifabutin; C020754:herbimycin; D019833:Genistein; D011505:Protein-Tyrosine Kinases