Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 May 1;90(9):4221–4225. doi: 10.1073/pnas.90.9.4221

Description of the leukocyte function-associated antigen 1 (LFA-1 or CD11a) promoter.

R D Cornwell 1, K A Gollahon 1, D D Hickstein 1
PMCID: PMC46478  PMID: 8097887

Abstract

The CD11a/CD18 (leukocyte function-associated antigen 1 or LFA-1) leukocyte integrin is expressed at high levels on the cell surface of T lymphocytes and macrophages, where it mediates homotypic and heterotypic adherence between leukocytes and other cell types by binding to intracellular adhesion molecules 1 and 2 on the conjugate cell. To initiate studies of the molecular regulation of expression of the CD11a molecule, we isolated genomic clones corresponding to the 5'-flanking region of CD11a, identified the transcriptional start sites for CD11a, and characterized the CD11a promoter sequence in transient expression assays. The CD11a promoter (1.7 kb) directed functional activity of a heterologous reporter gene in the T-lymphocyte cell line Jurkat and the myeloid cell line HL-60 but did not direct functional activity in three different nonleukocyte cell lines. Deletional analysis of the CD11a promoter sequence indicated the presence of distinct, cell-type-specific regulatory sequences with the region from -40 to -17 relative to the transcription start sites responsible for most of the in vitro activity of the CD11a promoter in the Jurkat T-cell line, and the promoter sequence located within the first 17 bp relative to the transcription start sites responsible for CD11a promoter activity in the HL-60 cell line. Identification of the CD11a promoter provides the opportunity to identify unique cis-acting elements and trans-acting factors responsible for the cell-type-specific expression of CD11a in human leukocytes. Further, the CD11a promoter may be useful in transgenic constructs and in retroviral vectors to direct expression of heterologous genes selectively in leukocytes.

Full text

PDF
4221

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Agura E. D., Howard M., Collins S. J. Identification and sequence analysis of the promoter for the leukocyte integrin beta-subunit (CD18): a retinoic acid-inducible gene. Blood. 1992 Feb 1;79(3):602–609. [PubMed] [Google Scholar]
  2. Arnaout M. A. Structure and function of the leukocyte adhesion molecules CD11/CD18. Blood. 1990 Mar 1;75(5):1037–1050. [PubMed] [Google Scholar]
  3. Briggs M. R., Kadonaga J. T., Bell S. P., Tjian R. Purification and biochemical characterization of the promoter-specific transcription factor, Sp1. Science. 1986 Oct 3;234(4772):47–52. doi: 10.1126/science.3529394. [DOI] [PubMed] [Google Scholar]
  4. Collins S. J., Gallo R. C., Gallagher R. E. Continuous growth and differentiation of human myeloid leukaemic cells in suspension culture. Nature. 1977 Nov 24;270(5635):347–349. doi: 10.1038/270347a0. [DOI] [PubMed] [Google Scholar]
  5. Corbi A. L., Larson R. S., Kishimoto T. K., Springer T. A., Morton C. C. Chromosomal location of the genes encoding the leukocyte adhesion receptors LFA-1, Mac-1 and p150,95. Identification of a gene cluster involved in cell adhesion. J Exp Med. 1988 May 1;167(5):1597–1607. doi: 10.1084/jem.167.5.1597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hickstein D. D., Baker D. M., Gollahon K. A., Back A. L. Identification of the promoter of the myelomonocytic leukocyte integrin CD11b. Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2105–2109. doi: 10.1073/pnas.89.6.2105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Jurka J., Smith T. A fundamental division in the Alu family of repeated sequences. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4775–4778. doi: 10.1073/pnas.85.13.4775. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Klemsz M. J., McKercher S. R., Celada A., Van Beveren C., Maki R. A. The macrophage and B cell-specific transcription factor PU.1 is related to the ets oncogene. Cell. 1990 Apr 6;61(1):113–124. doi: 10.1016/0092-8674(90)90219-5. [DOI] [PubMed] [Google Scholar]
  9. Landau N. R., St John T. P., Weissman I. L., Wolf S. C., Silverstone A. E., Baltimore D. Cloning of terminal transferase cDNA by antibody screening. Proc Natl Acad Sci U S A. 1984 Sep;81(18):5836–5840. doi: 10.1073/pnas.81.18.5836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Larson R. S., Corbi A. L., Berman L., Springer T. Primary structure of the leukocyte function-associated molecule-1 alpha subunit: an integrin with an embedded domain defining a protein superfamily. J Cell Biol. 1989 Feb;108(2):703–712. doi: 10.1083/jcb.108.2.703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Makgoba M. W., Sanders M. E., Ginther Luce G. E., Dustin M. L., Springer T. A., Clark E. A., Mannoni P., Shaw S. ICAM-1 a ligand for LFA-1-dependent adhesion of B, T and myeloid cells. Nature. 1988 Jan 7;331(6151):86–88. doi: 10.1038/331086a0. [DOI] [PubMed] [Google Scholar]
  12. McAllister R. M., Melnyk J., Finkelstein J. Z., Adams E. C., Jr, Gardner M. B. Cultivation in vitro of cells derived from a human rhabdomyosarcoma. Cancer. 1969 Sep;24(3):520–526. doi: 10.1002/1097-0142(196909)24:3<520::aid-cncr2820240313>3.0.co;2-m. [DOI] [PubMed] [Google Scholar]
  13. Mitchell P. J., Tjian R. Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins. Science. 1989 Jul 28;245(4916):371–378. doi: 10.1126/science.2667136. [DOI] [PubMed] [Google Scholar]
  14. Pugh B. F., Tjian R. Mechanism of transcriptional activation by Sp1: evidence for coactivators. Cell. 1990 Jun 29;61(7):1187–1197. doi: 10.1016/0092-8674(90)90683-6. [DOI] [PubMed] [Google Scholar]
  15. Sanchez-Madrid F., Nagy J. A., Robbins E., Simon P., Springer T. A. A human leukocyte differentiation antigen family with distinct alpha-subunits and a common beta-subunit: the lymphocyte function-associated antigen (LFA-1), the C3bi complement receptor (OKM1/Mac-1), and the p150,95 molecule. J Exp Med. 1983 Dec 1;158(6):1785–1803. doi: 10.1084/jem.158.6.1785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Sehgal A., Patil N., Chao M. A constitutive promoter directs expression of the nerve growth factor receptor gene. Mol Cell Biol. 1988 Aug;8(8):3160–3167. doi: 10.1128/mcb.8.8.3160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Smale S. T., Baltimore D. The "initiator" as a transcription control element. Cell. 1989 Apr 7;57(1):103–113. doi: 10.1016/0092-8674(89)90176-1. [DOI] [PubMed] [Google Scholar]
  18. Springer T. A. Adhesion receptors of the immune system. Nature. 1990 Aug 2;346(6283):425–434. doi: 10.1038/346425a0. [DOI] [PubMed] [Google Scholar]
  19. Staunton D. E., Dustin M. L., Springer T. A. Functional cloning of ICAM-2, a cell adhesion ligand for LFA-1 homologous to ICAM-1. Nature. 1989 May 4;339(6219):61–64. doi: 10.1038/339061a0. [DOI] [PubMed] [Google Scholar]
  20. Staunton D. E., Marlin S. D., Stratowa C., Dustin M. L., Springer T. A. Primary structure of ICAM-1 demonstrates interaction between members of the immunoglobulin and integrin supergene families. Cell. 1988 Mar 25;52(6):925–933. doi: 10.1016/0092-8674(88)90434-5. [DOI] [PubMed] [Google Scholar]
  21. Tom B. H., Rutzky L. P., Jakstys M. M., Oyasu R., Kaye C. I., Kahan B. D. Human colonic adenocarcinoma cells. I. Establishment and description of a new line. In Vitro. 1976 Mar;12(3):180–191. doi: 10.1007/BF02796440. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES