PMID- 1584769
OWN - NLM
STAT- MEDLINE
DCOM- 19920616
LR  - 20211203
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 89
IP  - 10
DP  - 1992 May 15
TI  - Evidence for a functional receptor for cyclosporin A on the surface of 
      lymphocytes.
PG  - 4353-7
AB  - Cyclosporin A (CsA) is an immunosuppressive agent that inhibits the synthesis of 
      lymphokines by T lymphocytes at the level of transcription. A cytoplasmic 
      protein, cyclophilin, is the most thoroughly studied CsA-binding protein, but its 
      ubiquitous presence in cells of all types raises questions about its role in 
      immunosuppression. In an attempt to ascertain the presence of a cell surface 
      receptor, we synthesized two polyvalent macromolecular CsA derivatives, 
      CsA-BBa-ovalbumin and CsA-BBa-aminodextran (CBD), from the product of the 
      photochemical reaction of CsA and 4-benzoylbenzoic acid (CsA-BBa). (i) They 
      inhibited the peptidylprolyl cis-trans isomerase activity of cyclophilin and the 
      synthesis of interleukin 2 by phorbol ester-activated EL-4 cells. (ii) CBD also 
      inhibited interleukin 2 secretion by Con A-activated T-cell-enriched mouse 
      splenocytes. 4-Benzoylbenzoic acid (BBa)-aminodextran and aminodextran were 
      inactive. (iii) Direct binding and competition studies with [3H]CsA indicated 
      that CBD does not enter EL-4 cells (i.e., it acted at the surface). (iv) CBD 
      caused agglutination of EL-4 cells, murine B and T lymphocytes, human thymocytes, 
      and two T-cell hybridomas. Agglutination was inhibited by a monoclonal antibody 
      to CsA and by CsA and CsA-BBa, but not by BBa. No agglutination was seen with 
      BBa-aminodextran or aminodextran. HeLa cells, Vero (monkey kidney) cells, a mouse 
      plasmacytoma, COS cells, and a poorly differentiated B-cell lymphoma were not 
      agglutinated. (v) EL-4 cells failed to be agglutinated after treatment with 
      trypsin or chymotrypsin. Specific agglutination was again possible after 
      incubation for 5 h at 37 degrees C in the absence of enzyme. (vi) CBD covalently 
      linked to crosslinked agarose beads inhibited interleukin 2 production by phorbol 
      ester-stimulated EL-4 cells. No activity was seen if cell-to-bead contact was 
      prevented by a 0.02-microns microporous filter that did not interfere with the 
      passage of CBD. Our findings support the presence of a functional receptor on the 
      surface of selected cells of the immune system.
FAU - Cacalano, N A
AU  - Cacalano NA
AD  - Department of Microbiology, Columbia University, New York, NY 10032.
FAU - Chen, B X
AU  - Chen BX
FAU - Cleveland, W L
AU  - Cleveland WL
FAU - Erlanger, B F
AU  - Erlanger BF
LA  - eng
GR  - P01-HL-36581/HL/NHLBI NIH HHS/United States
GR  - R01-DA-06333/DA/NIDA NIH HHS/United States
GR  - R01-NS-15581/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Interleukin-2)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (cyclosporin receptor)
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Animals
MH  - B-Lymphocytes/metabolism
MH  - Cell Line
MH  - Cell Membrane/immunology/metabolism
MH  - Cyclosporine/*metabolism/pharmacology
MH  - Humans
MH  - Immunosuppression Therapy
MH  - Interleukin-2/metabolism
MH  - Kinetics
MH  - Lymphocytes/drug effects/*immunology/metabolism
MH  - Mice
MH  - Receptors, Immunologic/*physiology
MH  - T-Lymphocytes/metabolism
MH  - Tetradecanoylphorbol Acetate/pharmacology
PMC - PMC49080
EDAT- 1992/05/15 00:00
MHDA- 1992/05/15 00:01
PMCR- 1992/11/15
CRDT- 1992/05/15 00:00
PHST- 1992/05/15 00:00 [pubmed]
PHST- 1992/05/15 00:01 [medline]
PHST- 1992/05/15 00:00 [entrez]
PHST- 1992/11/15 00:00 [pmc-release]
AID - 10.1073/pnas.89.10.4353 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1992 May 15;89(10):4353-7. doi: 
      10.1073/pnas.89.10.4353.