Tumor-promoting phorbol esters inhibit the binding of colony-stimulating factor (CSF-1) to murine peritoneal exudate macrophages

L-cell colony-stimulating factor (CSF-1) is a sialoglycoprotein of molecular weight 70,000 daltons that specifically stimulates macrophage colony formation by single committed cells from normal mouse bone marrow and by various classes of more differentiated tissue-derived mononuclear phagocyte colony-forming cells (Stanley et al., 1978). CSF-1 interacts with target cells by direct and specific binding to membrane receptors (CSF-1 receptors) that are present only on cells of the mononuclear phagocyte series and their precursors. We studied the effect of tumor-promoting phorbol esters on the binding of 125I-labeled CSF-1 (125I-CSF-1) to murine peritoneal exudate macrophages (PEM). Biologically active TPA (12-O-tetradecanoyl phorbol-13-acetate) inhibits the binding of 125I-CSF-1 to its receptor on PEM. This inhibition exhibits temperature, time, and concentration dependence. At 37 degrees C, maximum inhibition occurred at about 10(-7) M; inhibition was 50% at 5 X 10(-9) M. At 0 degrees C, the inhibitory activity of TPA is diminished. The action of TPA on PEM is transient. Treated cells recover their 125I-CSF-1-binding activity whether TPA is later removed or not. The process of recovering CSF-1-binding activity is completely blocked by the addition of cycloheximide. When several phorbol derivatives were tested for their inhibitory activities, only biologically active phorbol esters were found to possess such activities. Furthermore, the inhibitory activities of various phorbol esters are proportional to their tumor-promoting activities. Inhibition appears to be due to a reduction in the total number of available CSF-1 receptors rather than a decrease in receptor affinity.     

An analysis of the sensitivity of somatic cell hybrids to natural killer cell- and natural cytotoxic cell-mediated lysis

The analysis of the NK and NC sensitivity of somatic cell hybrids formed between parental cell lines that differ in their NK and NC sensitivity has shown the following. 1) The dominant expression of both NK and NC recognition determinants on target cells; 2) the dominant expression of two post-recognitive NC resistance mechanisms, one requiring protein synthesis and one being protein synthesis independent; and 3) the dominant expression of a post-recognitive NK resistance mechanism, which is protein synthesis independent. The post-recognitive protein synthesis-independent NC resistance mechanism confers no NK resistance and the post-recognitive NK resistance mechanism confers no NC resistance. Whether the post-recognitive protein synthesis-dependent NC resistance mechanism confers NK resistance remains open to question. The analysis of the hybrids indicates that transformed cells become sensitive to either NK- or NC-mediated lysis by losing their resistance to the lytic activity of these effector cells, and it appears that differentiation plays a role in determining whether NK or NC resistance will be lost upon transformation. A model is proposed in which the differentiation into a fibroblast associates the loss of NC resistance with transformation, whereas the differentiation into a lymphocyte associates the loss of NK resistance with transformation. Because the loss of NK resistance is not associated with the transformation of fibroblasts, they remain NK resistant, and because the transformation of lymphocytes is not associated with the loss of NC resistance, they remain NC resistant. This provides the basis for the target specificity exhibited by NK and NC effectors.     

Photosynthetic characteristics of Amaranthus tricolor,a C4 tropical leafy vegetable

The gas exchange characteristics are reported for Amaranthus tricolor, a C₄ vegetable amaranth of southeastern Asia. Maximum photosynthetic capacity was 48.3±1.0μmol CO₂ m^?2s^?1 and the temperature optimum was 35°C. The calculated intercellular CO₂ concentration at this leaf temperature and an incident photon flux (400–700 mm) of 2 mmol m^?2s^?1 averaged 208±14 μl l^?1, abnormally high for a C₄ species. The photosynthetic rate, intercellular CO₂ concentration, and leaf conductance all decreased with an increase in water vapor pressure deficit. However, the decrease in leaf conductance which resulted in a decrease in intercellular CO₂ concentration accounted for only one fourth of the observed decrease in photosynthetic rate as water vapor pressure deficit was increased. Subsequent measurements indicated that the depence of net photosynthesis on intercellular CO₂ concetration changed with water vapor pressure deficit.     

Lectin- and ionophore-stimulated Ca2+ influx in murine lymphocytes: inhibition by disialoganglioside

Gangliosides suppress lymphocyte mitogenesis when added exogenously to the cells. On the premise that the mechanism of ganglioside action may be an interference with primary induction events, mitogen-induced 45Ca2+ influx in murine lymphocytes was studied. Disialoganglioside (GD1a) at physiopathological concentrations inhibits concanavalin A-induced 45Ca2+ uptake as well as blast transformation. The suppressive action of GD1a is both concentration dependent (50% suppression at 13 microM) and very rapid (within 1 min). GD1a is not cytotoxic nor does it significantly alter the rate of Ca2+ efflux. The uptake studies were extended to A23187, a compound with mitogenic and specific divalent cation ionophore activities. Ca2+ uptake by lymphoid cells from AKR/J, Swiss, and CBA mice is stimulated by A23187; and GD1a, in a dose-dependent manner, inhibits the ionophore-induced 45Ca2+ influx. Pretreatment of thymocytes with GD1a renders the cells greatly insensitive to the subsequent ionophore activity of A23187. The results suggest that exogenous gangliosides may function as an inhibitor of some of the mitogen-triggered early events, including Ca2+ metabolism, and thus influence the immunological behavior of intact lymphoid cells.     

Microfluorometric detection of asymmetry in the centromeric region of mouse chromosomes

A lateral asymmetry in the centromeric region of mouse chromosomes is revealed in studies involving the BUdR quenching of 33258 Hoechst fluorescence. This cytologically detected asymmetry may reflect the unequal distribution of thymidine between the two chains of mouse satellite DNA.     

Mitotic chromosomes of species in the subgenusDrosophila (Diptera:Drosophilidae)

The karyotypes of 17 species in the subgenusDrosophila are compared according to their taxonomical relationships. Although closely related species often possess similar karyotypes, the karyotypes diverge considerably within the subgenus. Thus extensive chromosome rearrangements did occur during the speciation. Species with higher chromosome numbers do not necessarily have higher average of total chromosome length per cell.     

Une triple translocation chez le Triton Pleurodeles waltlii

A cytogenetic study has lead us to a stock of fertile heterozygotes for a triple translocation. The chromosomal rearrangement has first been detected in a female resulting from a cross between a normal female and a male submitted to X ray-irradiation. The aberration consists of rearrangements between a chromosome 3, a chromosome 6 and a chromosome 7. Abnormal chromosomes have the following constitution: 7q?: the terminal portion of the long arm is lost and replaced by the end of the short arm of the chromosome 3. 6 q+: the terminal portion of the long arm is lost and replaced by the end of the long arm of the chromosome 7. 3p+: the terminal portion of the short arm is lost and replaced by the end of the long arm of the chromosome 6. On the analogy of the human chromosome standardization, the formula of heterozygotes is 24, t (3p+, 6q+, 7q?). The first meiotic division shows both in the female and in the male 9 bivalents and one hexavalent. The formulae of the gametes are the same in both sexes. When a heterozygote is bred with a normal individual the offspring is composed of phenotypically normal or abnormal animals, depending on their karyotypes. The unbalanced karyotypes are lethal or semilethal. The importance of the malformations depends on the temperature of the water where the animals grow. The study of the meiotic slides brings a cytological confirmation of the results obtained from the study of the phenotypes and karyotypes which appear in the offspring.