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Epitope-specific signaling through CD45 on T lymphocytes leads to cAMP synthesis in monocytes after ICAM-1-dependent cellular interaction.

Publication ,  Journal Article
Lorenz, HM; Lagoo, AS; Lagoo-Deenadalayan, SA; Barber, WH; Kalden, JR; Hardy, KJ
Published in: Eur J Immunol
August 1998

We recently demonstrated that different CD45 monoclonal antibodies (mAb) are able to induce cellular aggregation in human peripheral blood mononuclear cells (PBMC) through LFA-1/ICAM-1 interactions. Such interactions could be down-modulated by protein kinase (PK) A/G inhibitors, but were unaffected by inhibitors of PKC, suggesting the involvement of PKA or PKG in CD45 mAb-induced adhesion. In this study we show that after incubation of PBMC with several (but not all) mAb to CD45, CD45RO and CD45RA, intracellular cAMP, but not cGMP concentrations readily increase, reaching a maximum 30 min after start of activation. As evidenced by several lines of investigation cAMP accumulation was independent of Fc receptor-associated signaling as well as tyrosine phosphatase activity of CD45. In highly pure T lymphocytes, CD45 mAb were unable to induce cAMP synthesis, but readily did so after addition of autologous monocytes. After paraformaldehyde fixation of both quiescent or IFN-gamma/TNF-alpha-preactivated monocytes, cAMP production was no longer detectable, suggesting monocytes as the cell of origin for the increased cAMP synthesis. Further, cAMP accumulation in monocytes occurred after reconstitution to T lymphocytes preincubated with CD45 mAb and extensively washed. Importantly, pretreatment of T lymphocyte/monocyte mixtures with LFA-1 mAb and/or ICAM-1 mAb down-regulated CD45 mAb-induced cAMP synthesis. Finally, we demonstrate that CD45 mAb are not only capable of inducing cAMP production, but also of directly stimulating PKA enzyme activity. Based on the data presented, we propose that CD45 signaling in T lymphocytes subsequently activates cAMP accumulation and PKA activation in monocytes via LFA-1/ICAM-1-dependent cellular interactions.

Duke Scholars

Published In

Eur J Immunol

DOI

ISSN

0014-2980

Publication Date

August 1998

Volume

28

Issue

8

Start / End Page

2300 / 2310

Location

Germany

Related Subject Headings

  • T-Lymphocytes
  • Signal Transduction
  • Monocytes
  • Lymphocyte Function-Associated Antigen-1
  • Leukocyte Common Antigens
  • Intercellular Adhesion Molecule-1
  • In Vitro Techniques
  • Immunology
  • Humans
  • Epitopes
 

Citation

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Lorenz, H. M., Lagoo, A. S., Lagoo-Deenadalayan, S. A., Barber, W. H., Kalden, J. R., & Hardy, K. J. (1998). Epitope-specific signaling through CD45 on T lymphocytes leads to cAMP synthesis in monocytes after ICAM-1-dependent cellular interaction. Eur J Immunol, 28(8), 2300–2310. https://doi.org/10.1002/(SICI)1521-4141(199808)28:08<2300::AID-IMMU2300>3.0.CO;2-O
Lorenz, H. M., A. S. Lagoo, S. A. Lagoo-Deenadalayan, W. H. Barber, J. R. Kalden, and K. J. Hardy. “Epitope-specific signaling through CD45 on T lymphocytes leads to cAMP synthesis in monocytes after ICAM-1-dependent cellular interaction.Eur J Immunol 28, no. 8 (August 1998): 2300–2310. https://doi.org/10.1002/(SICI)1521-4141(199808)28:08<2300::AID-IMMU2300>3.0.CO;2-O.
Lorenz HM, Lagoo AS, Lagoo-Deenadalayan SA, Barber WH, Kalden JR, Hardy KJ. Epitope-specific signaling through CD45 on T lymphocytes leads to cAMP synthesis in monocytes after ICAM-1-dependent cellular interaction. Eur J Immunol. 1998 Aug;28(8):2300–10.
Lorenz, H. M., et al. “Epitope-specific signaling through CD45 on T lymphocytes leads to cAMP synthesis in monocytes after ICAM-1-dependent cellular interaction.Eur J Immunol, vol. 28, no. 8, Aug. 1998, pp. 2300–10. Pubmed, doi:10.1002/(SICI)1521-4141(199808)28:08<2300::AID-IMMU2300>3.0.CO;2-O.
Lorenz HM, Lagoo AS, Lagoo-Deenadalayan SA, Barber WH, Kalden JR, Hardy KJ. Epitope-specific signaling through CD45 on T lymphocytes leads to cAMP synthesis in monocytes after ICAM-1-dependent cellular interaction. Eur J Immunol. 1998 Aug;28(8):2300–2310.
Journal cover image

Published In

Eur J Immunol

DOI

ISSN

0014-2980

Publication Date

August 1998

Volume

28

Issue

8

Start / End Page

2300 / 2310

Location

Germany

Related Subject Headings

  • T-Lymphocytes
  • Signal Transduction
  • Monocytes
  • Lymphocyte Function-Associated Antigen-1
  • Leukocyte Common Antigens
  • Intercellular Adhesion Molecule-1
  • In Vitro Techniques
  • Immunology
  • Humans
  • Epitopes