Ligand activation of nerve growth factor receptor TrkA protects monocytes from apoptosis.
Nerve growth factor (NGF) receptors are expressed in different cell types outside the nervous system, and increasing evidence indicates that NGF can act as a regulatory molecule during inflammatory and immune responses. In this study, we show that triggering of the high-affinity NGF receptor TrkA with agonists protects monocytes from apoptosis induced by gliotoxin or UVB radiation. TrkA stimulation up-regulates the expression of the anti-apoptotic Bcl-2 family members, Bcl-2, Bcl-XL, and Bfl-1. On the other hand, TrkA stimulation does not change the expression of MHC, CD80, CD86, CD40, and CD54 molecules, nor the antigen-presenting function of monocytes. In addition, during in vitro monocyte to dendritic cell differentiation TrkA expression is progressively lost, suggesting that NGF selectively affects monocyte but not dendritic cell survival.
Laboratory of Immunology, Istituto Dermopatico dell'Immacolata, IRCCS, Rome, Italy. lasala@idi.it
A
A
la Sala
S
S
Corinti
M
M
Federici
H U
HU
Saragovi
G
G
Girolomoni
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017951:Antigen Presentation / Q000187:drug effects; D015703:Antigens, CD / Q000096:biosynthesis; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D002227:Carbazoles / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology; D005786:Gene Expression Regulation / Q000187:drug effects; D019254:Genes, bcl-2 / Q000187:drug effects; D005912:Gliotoxin / Q000633:toxicity; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D026121:Indole Alkaloids; D015847:Interleukin-4 / Q000494:pharmacology; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D015778:Minor Histocompatibility Antigens; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects; D009414:Nerve Growth Factors / Q000494:pharmacology*; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D020917:Receptor, trkA / Q000819:agonists* / Q000502:physiology; D014466:Ultraviolet Rays / Q000009:adverse effects; D051020:bcl-X Protein
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C096816:BCL2-related protein A1; C494811:BCL2L1 protein, human; D002227:Carbazoles; D026121:Indole Alkaloids; D008024:Ligands; D008070:Lipopolysaccharides; D015778:Minor Histocompatibility Antigens; D009414:Nerve Growth Factors; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D015847:Interleukin-4; D005912:Gliotoxin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C049985:staurosporine aglycone; D020917:Receptor, trkA