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Biomedical subjects

I Lemaire

Publications and source records attributed to I Lemaire.

63 records · Page 4Linked to original sources
PubMed1977

Coexpression of mutant and wild type protein kinase in lymphoma cells resistant to dibutyryl cyclic AMP.

A mutant clone resistant to dibutyryl cyclic AMP was isolated from S49 mouse lymphoma cells. The mutant expressed a form of cyclic AMP-dependent protein kinase distinguishable from wild type kinase by its decreased sensitivity to activation by cyclic AMP and its increased thermal lability. Hybrids formed between mutant and wild type cells were resistant to dibutyryl cyclic AMP and expressed both mutant and wild type activities in about equal amount. The parent mutant cells also appeared to express wild type kinase activity, but at a lower level. We conclude that wild type S49 cells have and express two identical alleles for the regulatory subunit of protein kinase, one of which has undergone mutation in the mutant cells.

Bucladesine↗
PubMed1977

Cyclic AMP-induced cytolysis in S49 cells: selection of an unresponsive "deathless" mutant.

Wild-type S49 lymphoma cells respond to cyclic adenosine 3', 5'-monophosphate (cAMP) by inducing cAMP phosphodiesterase, halting growth in the G1 phase of the cell cycle and subsequently dying. By using a counter selection procedure, we have isolated a new class of mutants of S49 cells termed "deathless" that are resistant to cytolysis, but otherwise respond like the wild-type cells to cAMP. Upon removal of the cyclic nucleotide, D-cells resume their normal growth. Unlike all other cAMP-resistant mutants of S49 cells isolated until now, the D- mutant has a functionally normal cAMP-dependent protein kinase and retains normal ability to induce phosphodiesterase and arrest cell growth in G1. It is probable that the altered gene product of the D- mutant is distal to protein kinase and in a biochemical pathway separate from that of cAMP induction of phosphodiesterase or growth arrest. The D- mutant may facilitate studies of the mechanism of cAMP-induced cytolysis and growth regulation in S49 cells.

Animals↗
PubMedDate not supplied

Alveolar macrophage inhibition of lung-associated NK activity: involvement of prostaglandins and transforming growth factor-beta 1.

Natural killer (NK) activity plays an important role in host defense. It is likely that this defensive role is shaped by compartmental and local environmental factors. The present study investigated the regulatory effects of alveolar macrophages (AM) on lung-associated NK activity. AM and lung lymphocytes (LL) were permitted to interact in a two-chamber system which prohibited cell contact but supported diffusion of soluble factors. AM were found to inhibit NK activity from LL in a time-dependent and reversible manner. The inhibitory event was shown to be mediated by soluble factors acting upon a post-binding event(s) in the lytic pathway of LL. AM inhibition was sensitive to indomethacin treatment (10(-5) M), which caused a decrease in prostaglandin E2 (PGE2) concentrations. Quantitation of PGE2 levels and treatment of LL with exogenous PGE2 indicated that the inhibitory effect could not be exclusively due to PGE2. It was subsequently found that exogenous transforming growth factor-beta 1 (TGF-beta 1) also inhibited LL NK activity and that treatment of inhibitory AM supernatant with a neutralizing antibody to TGF-beta 1 adsorbs up to 55% of its inhibitory activity. Moreover, the amount of TGF-beta 1 found in AM-LL co-culture media (25 pg/mL) correlated well with the level of NK inhibition observed. By contrast, platelet-derived growth factor and nitric oxide did not play a significant role in mediating AM suppression. Taken together, the data suggest that AM inhibit lung NK activity by interfering with post-binding lytic event(s) through the production of PGE2 and TGF-beta 1.

Animals↗
PubMedDate not supplied

Effects of hyperthermia on natural killer cells: inhibition of lytic function and microtubule organization.

Cells with natural killer activity (NK) may play an important role in host defence against tumour cells. The lytic function of NK cells is very sensitive to hyperthermic inactivation. However, cells with NK activity isolated from rat spleen and exposed to 41-42.5 degrees C for 30 min could partially recover their cytotoxic activity after incubation at 37 degrees C. The recovered cytotoxicity was still NK-specific, as it only resulted in the lysis of YAC-1 sensitive targets, and could not lyse NK-resistant P815 mastocytoma cells. Conjugate formation assay using NK cells labelled with specific monoclonal antibody (mAb) 3.2.3 indicated that the binding of NK cells to targets was not significantly affected by heat treatment. Compared to controls, however, microtubule organizing centre (MTOC) reorientation towards the region of intercellular contact was reduced by 40% in heated effector cells. This was accompanied by a greater inhibition (62-77%) of NK lytic activity. Kinetic analysis indicated that MTOC reorientation capacity recovered following incubation at 37 degrees C. MTOC recovery was maximal 4 h after treatment whereas that of lytic activity peaked at 6 h. These data indicate that NK cells recover NK-specific lytic activity after heat inactivation. Moreover, our study demonstrates that hyperthermia interferes with post-binding MTOC reorientation, and further supports a role for microtubule in secretory processes involved in NK-mediated cytolysis.

Animals↗
PubMedDate not supplied

Comparative analysis of natural killer function in lung, spleen, and peripheral blood lymphocytes: evidence of differential characteristics.

Organ associated as well as systemic natural killer (NK) activity play an important role in host defense. It is likely that tissue NK cells exhibit some specific characteristics resulting from their local environment. The purpose of the present study was to compare NK cell function of rat lung to that of spleen and blood in terms of magnitude of NK activity, NK cell number, and response to biological response modifiers (BRM). Lung interstitial lymphocytes (LL) were found to display significant cytotoxicity which was selective for YAC-1 tumor cells and abolished by treatment with antiasialo GM-1 serum and L-leucine methyl ester. In addition, LL were more effective than peripheral blood lymphocytes (PBL) and spleen lymphocytes (SL), although LL contained the same proportion of NK 3.2.3 positive cells than the spleen. Furthermore, the in vitro response to BRM varied both with BRM used and effector cell origin. Human recombinant interleukin 2 (rIL-2) increased NK activity of LL and PBL to a similar extent, whereas SL were more responsive to such treatment. Interferon alpha/beta (IFN-alpha/beta) increased NK activity in all three compartments with PBL being less responsive. By contrast, rat recombinant interferon gamma (rIFN-gamma) failed to augment LL or SL NK activity but did result in a significant enhancement of PBL activity. Together these data indicate that the lung contains comparable numbers of NK cells to that of spleen but which display higher specific activity. Furthermore, NK cell response to BRM vary with tissue origin, suggesting that tissue specific response may be an important determinant for the effective use of BRM.

Animals↗
PubMedDate not supplied

Effects of chrysotile asbestos on DNA synthesis and growth of human embryonic lung fibroblasts.

The in vitro effects of asbestos fibers on thymidine (TdR3H) incorporation and growth of lung fibroblasts have been studied. Incubation of human embryonic lung fibroblasts with UICC Chrysotile B asbestos for 48 hr caused a 3 to 5-fold increase of TdR3H incorporation as compared with control cultures. This increase was dose-dependent with optimal effect obtained with doses as low as 10 micrograms/ml and with cell density of 5 X 10(4) fibroblasts per culture. However, enhanced TdR3H incorporation in treated cells was not correlated with an overall increase of the fibroblast population compared with control cultures as evidenced by cell counts and microscopic examination. Fibroblasts exposed to relatively low concentrations of UICC chrysotile (5-10 micrograms/ml) displayed an initial decrease in cell number compared to controls during the first 24 hr of incubation. At 48 hr however, enhanced TdR3H incorporation occurred with a concomittant increase in cell number. Moreover, continuous exposure of fibroblast cultures to chrysotile (10 micrograms/ml) for a longer period of time led to sustained increase of TdR3H incorporation and resumption of cell proliferation. It is suggested that increased thymidine incorporation is directly related to the effectiveness of asbestos in inhibiting the growth of lung fibroblasts and that measurement of TdR3H incorporation may represent a sensitive means of assessing rapidly the biological activity of asbestos. The possible relevance of this activity to asbestos-induced fibrogenesis and tumorigenesis is also discussed.

Asbestos↗