Mechanisms of CD47-induced caspase-independent cell death in normal and leukemic cells: link between phosphatidylserine exposure and cytoskeleton organization.

Dying cells, apoptotic or necrotic, are swiftly eliminated by professional phagocytes. We previously reported that CD47 engagement by CD47 mAb or thrombospondin induced caspase-independent cell death of chronic lymphocytic leukemic B cells (B-CLL). Here we show that human immature dendritic cells (iDCs) phagocytosed the CD47 mAb-killed leukemic cells in the absence of caspases 3, 7, 8, and 9 activation in the malignant lymphocytes.

CD47 ligation induces caspase-independent cell death in chronic lymphocytic leukemia.

Thrombospondin forms a 'molecular bridge' between phagocytic and apoptotic cells through interaction with alphavbeta3/CD36. We report here that engagement of CD47, a newly described thrombospondin receptor, by immobilized monoclonal antibody against CD47 or by thrombospondin induced in all B-cell chronic lymphocytic leukemia clones the cytoplasmic features of apoptosis (cell shrinkage, decrease in mitochondrial transmembrane potential and phosphatidylserine externalization) without the nuclear features (chromatin condensation, appearance of single-stranded DNA, DNA fragmentation and cleavage of poly ADP-ribose polymerase). These cytoplasmic events of apoptosis were not prevented by the addition of caspase inhibitor z-VAD-fmk, or by the presence of survival factors (such as interleukin-4 and gamma interferon) or cell activation.

Prognostic importance of serum soluble CD23 level in chronic lymphocytic leukemia.

Prognosis of B-cell chronic lymphocytic leukemia (CLL) is based on clinical staging whose limitation is the failure to assess whether the disease will progress or remain stable in early stage (Binet A, or Rai 0, I, II) patients. We previously reported that soluble CD23 (sCD23), a protein derived from the B-cell membrane CD23 Ag, is selectively elevated in the serum of CLL patients. This prospective study assessed the predictive value of serum sCD23 level measured at study entry on the overall survival of all CLL patients and on disease progression of stage Binet A patients.

The two CD23 isoforms display differential regulation in chronic lymphocytic leukaemia.

B lymphocytes from chronic lymphocytic leukaemia (B-CLL) patients express the two CD23 isoforms (type A and B), which differ only in their intracytoplasmic domain. The abnormal regulation of the CD23 antigen in response to IL-4, IFNs alpha and gamma results in CD23 over-expression on B-CLL cells. Our present study shows that the two CD23 isoforms are differentially and abnormally regulated on B-CLL cells.

Interleukin 4 protects chronic lymphocytic leukemic B cells from death by apoptosis and upregulates Bcl-2 expression.

B chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation of slow-dividing and long-lived monoclonal B cells arrested at the intermediate stage of their differentiation. We previously showed that interleukin 4 (IL-4) not only inhibits but also prevents the proliferation of B-CLL cells. We report here that IL-4 protects the B-CLL cells from death by apoptosis (programmed cell death [PCD]).

Low-molecular weight B cell growth factor (BCGF-12KD) as an autocrine growth factor in B cell chronic lymphocytic leukemia.

The role of cytokines in the growth and spreading of human hematologic malignancies has been underlined in recent years. Here we report evidence that a human 12-kDa B cell growth factor (BCGF-12KD) may function as a growth stimulatory factor in B cell chronic lymphocytic leukemia (B-CLL). First, recombinant BCGF-12KD induced dose-dependent DNA synthesis in neoplastic B cells of four B-CLL patients tested.

CD23 antigen regulation and signaling in chronic lymphocytic leukemia.

B lymphocytes from patients with chronic lymphocytic leukemia (B-CLLs), strongly express the CD23 antigen, a surface marker with significant prognostic importance in this disease. Because we previously reported that IL-4 shows a poor capacity for CD23 expression on B-CLLs, we first examined the possible mechanisms underlying CD23 overexpression on B-CLLs and found that mitogen-activated CLL T cells release soluble factors that are capable, in synergy with IL-4, of strongly inducing CD23. Using neutralizing Abs, we noticed that the T-cell-derived enhancing activity is entirely ascribed to the combined effects of IFN gamma (potent inhibitor of CD23 on normal B cells), TNF alpha (which has no effect on normal B cells), and IL-2 (which has a slight enhancing effect on both CLL and normal B cells).

Antiproliferative effect of interleukin-4 in B chronic lymphocytic leukemia.

Recombinant interleukin-4 (IL-4) profoundly inhibits the proliferative response of chronic lymphocytic leukemic B cells (B-CLLs) to recombinant interleukin-2 (IL-2). In the present study, we confirmed and extended these data by showing that IL-4 strongly suppresses the [3H]thymidine incorporation by B-CLLs stimulated by recombinant tumor necrosis factor alpha, recombinant interferon alpha, IL-2, and low molecular weight B cell growth factor in the absence of costimulant. Recombinant interleukin-4 inhibits spontaneous DNA synthesis suggesting that it also interferes with the autocrine proliferation of these cells.

The in vivo expression of type B CD23 mRNA in B-chronic lymphocytic leukemic cells is associated with an abnormally low CD23 upregulation by IL-4: comparison with their normal cellular counterparts.

We recently reported that the sera of chronic lymphocytic leukemia (CLL) patients contained 3-500 times more soluble CD23 (or IgE-BF) than the sera of patients with other lymphoproliferative diseases or normal individuals and that their B cells (B-CLLs) overexpressed CD23 Ag. In the present report, we extended these studies and showed that CD5+ B cells from all CLL patients (n = 15) co-express CD23 Ag. We next identified two additional major differences between B-CLLs and normal adult B cells.

Expression of CD23 antigen and its regulation by IL-4 in chronic lymphocytic leukemia.

In our previous studies, we reported that the sera from CLL patients contain 3 to 500 times more IgE-BFs (or soluble CD23) than the sera from normal individuals (Sarfati M., Bron D., Lagneaux L.

Inhibition of marginal leakage with a dentin bonding agent.

Class V cavity preparations were treated in vitro with dentin bonding agents and composite. The teeth were thermally cycled, stained, and scored for marginal leakage, by a silver stain technique. The composite-only control group leaked significantly more than did the dentin-bonding-treated experimental groups.

Marginal leakage of class V cavity preparations.

Dentin-bonding materials, ferric oxylate (FO), addition reaction between N-phenylglycine and glycidyl methacrylate (NPG-GMA), and addition reaction product of pyromellitic acid dianhydride and 2-hydroxyethyl methacrylate (PMDM), were tested together for their ability to inhibit marginal leakage in Class V composite restorations in vitro. Sixteen experimental teeth were pretreated with FO, NPG-GMA, PMDM, and restored with composite. Sixteen control teeth were treated conventionally with composite.

Seroimmunity following vaccination in infants by an inactivated poliovirus vaccine prepared on Vero cells.

An inactivated poliovirus vaccine prepared from cultures of Vero cells has been tested on 61 infants from two to 11 months of age (mean age, 4.3 months) for tolerance and serologic potency. Three doses of vaccine were given one month apart at the same time that diphtheria-tetanus-pertussis vaccine was injected at another body site.

[Serotype 5 pneumococcus in epidemiology and vaccine].

The Streptococcus pneumoniae serotype 5 is commonly isolated in human pathology. In France, it is the fourth pneumococcal serotype for acute pneumonia (9.1%) and bacteremia (6.

[Attempts at time-related control of bovine hypodermiasis at scattered or grouped farms].

The control was performed by a unic systemic autumn treatment on heifers and repeated topical spring treatments on dairy cows. After a four years programme, limited success are obtained. No difference in the efficacy are observed in isolated or grouped farms.