Modulation of pro- and anti-apoptotic genes in lymphocytes exposed to bone cements.
The ability of bone cements to modify the apoptotic program in activated immune cells and the mechanisms by which they act were evaluated. Mononuclear cells were collected from healthy individuals, cultured for 4 and 24 h with phytohemoagglutinina-P and cement extracts and then tested to assess: (a) cell viability; (b) early apoptotic events, by Annexin V/propidium iodide staining; and (c) the expression of pro- (p53, c-myc, ICE) and anti-apoptotic (bcl-2) genes. After 4 h three cements were able to increase significantly the percentage of apoptotic cells, while after 24 h no differences were found. The proportion of dead cells was not significantly changed at either culture time. The simultaneous expression of both pro-apoptotic (ICE, c-myc, p53) and antiapoptotic genes (bcl-2) was investigated only with regard to the materials which induced significant changes in apoptosis: two cements induced the p53 expression, while the third down-regulated bcl-2. As apoptosis regulates the balance of immune response, the authors recommend that the interaction between materials and immune cells should be assessed, so that the use of pro-apoptotic materials may be avoided in patients with immune defects.
Granchi
D
D
Laboratorio di Fisiopotologia Degli Impianti Ortopedici, Bologna, Italy. donatella.granchi@ior.it
Ciapetti
G
G
Filippini
F
F
Stea
S
S
Cenni
E
E
Pizzoferrato
A
A
Toni
A
A
D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D001843:Bone Cements / Q000494:pharmacology; D020170:Caspase 1 / Q000096:biosynthesis / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D005434:Flow Cytometry; D019254:Genes, bcl-2 / Q000235:genetics; D016259:Genes, myc / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000473:pathology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011419:Propidium / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D012313:RNA / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D017304:Annexin A5; D001843:Bone Cements; D010835:Phytohemagglutinins; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53; C028784:phytohemagglutinin-P; D011419:Propidium; D012313:RNA; D020170:Caspase 1