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Biomedical subjects

I Lemaire

Publications and source records attributed to I Lemaire.

At least 55 records · Page 3Linked to original sources
PubMed1983

Asbestos exposure enhances the release of fibroblast growth factor by sheep alveolar macrophages.

Interaction between free airway cells (FAC) and lung fibroblasts was studied in a sheep model of asbestosis. Three groups of six sheep each received, respectively, by repeated intratracheal instillations, saline (control), 328 mg (low dose), and 2282 mg (high dose) of UICC chrysotile B asbestos. Sixteen months after the first instillation, FAC obtained by segmental bronchoalveolar lavage (BAL) of sheep in each group were incubated for various intervals, and the effect of their culture supernatants (FAC-SN) on human embryonic lung fibroblast proliferation was determined. FAC-SN from control animals stimulated thymidine (3H-TdR) incorporation by lung fibroblasts two- to threefold compared to untreated cultures. Maximal stimulation was observed at 48 hr and was correlated with a significant increase of the fibroblast population at 72 hr. FAC population from control sheep consisted primarily of macrophages (79%) and lymphocytes (15%), and separation of these two cell populations indicated that only macrophages produced the fibroblast-stimulating activity. Production occurred within 1 hr of incubation and was maximal between 2 and 4 hr. This activity was nondialyzable and stable at 56 degrees C for 30 min, but was destroyed at 80 degrees C and low pH. Moreover, FAC-SN from sheep exposed to asbestos stimulated 3H-TdR incorporation by fibroblasts five- to sixfold compared to two- to threefold for control FAC-SN. This activity may modulate fibrogenesis and may be involved in the eventual fibrogenic response to asbestos.

Animals↗
PubMed1983

In vitro suppression of fibroblast growth inhibitory lymphokine production by asbestos.

Human peripheral blood mononuclear leucocytes (PBML) stimulated with concanavalin A (Con A) or phytohaemagglutinin (PHA) produced a soluble factor which inhibits lung fibroblast DNA synthesis and growth. Lymphocyte enriched preparations produced significant growth inhibitory activity in the presence of PHA whereas media from adherent mononuclear cells incubated in the presence of the mitogen did not contain similar activity. This fibroblast growth inhibitory factor (FGIF) was non-dialysable, heat stable and resistant to pH 5. FGIF was also resistant to treatment with chymotrypsin and phosphodiesterase but partially sensitive to treatment with trypsin. Interestingly, there was significant suppression of FGIF production by PBML cultured with PHA in the presence of low concentrations of chrysotile asbestos (5-25 micrograms/ml). In this regard, asbestos (25 micrograms/ml) was not cytotoxic for lymphocytes but had a damaging effect on monocytes as evidenced by the release of lactate dehydrogenase (LDH) a cytoplasmic enzyme, in their culture media. These findings indicate that stimulated lymphocytes have the ability to inhibit fibroblast proliferation by releasing FGIF and that asbestos interfere with this process. Thus, while FGIF may regulate the extent of connective tissue proliferation during normal repair process, suppression of its production by asbestos may contribute to excessive fibroblast accumulation and fibrosis.

Asbestos↗
PubMed1982

Asbestos related changes in pulmonary and systemic immune responses--early enhancement followed by inhibition.

We recently developed an animal model in order to study the pulmonary and systemic reactions following exposure to environmental pollutants. In this model, conscious sheep received repeated intratracheal instillations of a suspension of 0 (controls), 2mg (low dose) or 128 mg (high dose) of chrysotile asbestos fibres over a 12 month period. A significant dose-dependent enhancement in proliferative responses of pulmonary free airway cells (FAC) to four mitogens was observed after a first instillation. A somewhat weaker stimulation was also observed in peripheral blood mononuclear leucocytes (PBML). At 6 months, the high dose animals no longer displayed the dose-dependent enhancement of FAC responses and manifested actual depression of PBML responses. At 12 months, all asbestos exposed animals showed impaired responses of FAC, whereas only the PBML of high dose animals were showing such an impairment. These data suggest that asbestos exposure has a dose-dependent initial enhancement of local pulmonary as well as systemic responses to mitogens while prolonged exposure and higher doses can subsequently lead to a relative depression of local and systemic cellular immune activity. Although responsive early after asbestos exposure, systemic immunity appears to lag behind local immunity in the late depressive effect of asbestos fibres on mitogen responsiveness. In addition to these cell-directed effects serum factors seem to play an inhibitory role in lymphocyte responses to mitogens in animals repeatedly exposed to asbestos.

Animals↗
PubMed1981

Distinct regulations by calcium of cyclic GMP levels and catecholamine secretion in isolated bovine adrenal chromaffin cells.

The effects of various calcium-dependent secretagogues on cyclic GMP levels and catecholamine (CA) secretion were measured in a preparation of bovine adrenal chromaffin cells. The secretory effect of acetylcholine (ACh; 8--10 fold stimulation) was mimicked by nicotine but not muscarine. Three--five fold stimulations of cyclic GMP levels were also obtained with ACh and muscarine but not nicotine. High concentration of K+, and the ionophore A23187, also elevated cyclic GMP levels. However, secretion produced by veratridine, ouabain, and the ionophore X537A was not accompanied by any rise in cyclic GMP levels. Removal of extracellular calcium significantly decreased both basal levels of CA secretion and of cyclic GMP and completely abolished their stimulation by ACh. The half-maximal effects of calcium on the cholinergic stimulations of cyclic GMP levels and of CA secretion were observed at 0.2 and 2.5 mM, respectively. Substitution of Ca2+ by Sr2+ was more effective in maintaining the cyclic GMP response than the secretory response. The calcium channel blockers Co2+, Mg2+ and Ni2+ inhibited the cholinergic stimulation of cyclic GMP more than that of CA release. On the other hand, the organic calcium channel blockers, verapamil and methoxyverapamil (D--600) were more effective antagonists of the secretory response. These data indicate that the cholinergic stimulations of CA secretion and of cyclic GMP levels in bovine adrenal chromaffin cells are regulated by calcium via two distinct mechanisms.

Adrenal Glands↗
PubMed1981

Studies on the inhibitory action of opiate compounds in isolated bovine adrenal chromaffin cells: noninvolvement of stereospecific opiate binding sites.

In isolated bovine adrenal chromaffin cells, beta-endorphin, dynorphin, and levorphanol caused a dose-dependent inhibition of catecholamine (CA) secretion elicited by acetylcholine (ACh), with an ID50 of 50, 1.3, and 4.3 microM, respectively. The inhibition by the opiate compounds was specific for the release evoked by ACh and nicotinic drugs and was noncompetitive with ACh. Stereospecific binding sites for the opiate agonist [3H]etorphine were found in homogenates of bovine adrenal medulla (KD = 0.59 nM). beta-Endorphin, dynorphin, levorphanol, and naloxone were potent inhibitors of the binding of [3H]etorphine with an ID50 of 12, 0.4, 5.2, and 6.2 nM, respectively. However, [3,5-I2Tyr1]-beta-endorphin, [3,5-I2Tyr1]-dynorphin, and dextrorphan, three opiate compounds with no or little activity in the guinea pig ileum assay, were relatively ineffective in inhibiting the binding of [3H]etorphine (ID50 700, 600, and 10,000 nM, respectively). On the other hand, these three compounds were equipotent with beta-endorphin, dynorphin, and levorphanol, respectively, in inhibiting the ACh-evoked release of CA from the adrenal chromaffin cells (ID50 of 10, 1.5, and 6 microM, respectively). Inhibition of CA release was also obtained with naloxone (ID50 = 14) microM) and naltrexone (ID50 greater than 10(-4) M), two classical antagonists of opiate receptors, and this effect was additive to that of beta-endorphin. These data indicate that the opiate modulation of CA release from adrenal chromaffin cells is not related to the stimulation of the high affinity stereospecific opiate binding sites of the adrenal medulla. The physiological function of these sites remains to be determined.

Acetylcholine↗
PubMed1981

Significant increases of cyclic AMP and alkaline phosphatase in bronchoalveolar lavage fluids of sheep exposed to asbestos.

Exposure to asbestos for six months caused a significant increase of adenosine 3',5'-cyclic monophosphate (cAMP) levels (2-fold in bronchoalveolar lavage (BAL) fluids of sheep with no significant change in guanosine 3',5'-cyclic monophosphate (cGMP) and alkaline phosphatase (AP) activity. When exposure was prolonged for another 3 month-period, the increase in cAMP levels persisted and was accompanied by a 4-fold stimulation of AP activity, and enzyme associated with the surfactant fraction of BAL fluids.

Alkaline Phosphatase↗
PubMed1981

Early effects of low-doses exposure to asbestos on local cellular immune responses in the lung.

We recently developed an animal model to study the pulmonary reactions after exposure to environmental pollutants. In this model, sheep received monthly intratracheal instillations of a suspension of varying amounts of chrysotile asbestos in saline. All animals were studied by pulmonary function tests, transbronchial biopsies, and bronchoalveolar lavage. During the 6 mo of the study, no changes were seen in the 2 former tests, but bronchoalveolar lavage yielded leukocytes that responded with enhanced proliferative activity to concanavalin A, pokeweed mitogen, and staphylococcal lysate. The response to phytohemagglutinin was poor but also enhanced in the asbestos-exposed animals. Enhanced responsiveness was dose-related, except for the highest dose used, 128 mg, which was associated with a less enhanced proliferative response or none. Our data suggest that the initial response to low-dose exposure to asbestos consists in a stimulation of lymphocyte function; the possibility that this phenomenon may be linked to the eventual fibrogenic response of asbestosis warrants further studies.

Animals↗
PubMed1978

Systemic administration of beta-endorphin: potent hypotensive effect involving a serotonergic pathway.

In normal adult rats anesthetized with urethane, intravenous injections of beta-endorphin (30--150 micrograms kg-1) induced a transient fall of blood pressure followed by a small hypertension and a prolonged hypotension. Prior administration of naloxone completely blocked these effects, whereas naloxone, given 1 hr after beta-endorphin, did not reverse the prolonged depressor phase of the opioid peptide. The effects of beta-endorphin on the arterial blood pressure were greatly reduced in animals pretreated with p-chlorophenylalanine, a specific depletor of serotonin. Moreover, in rats pretreated with potent serotonin antagonists such as cyproheptadine, mianserin, and metergoline, beta-endorphin did not produce a significant hypotension. Furthermore, the depressor effect of beta-endorphin was potentiated by fluoxetine, a specific serotonin uptake inhibitor. These observations suggest the participation of a serotonergic pathway in the action of beta-endorphin on the arterial blood pressure.

Blood Pressure↗