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Biomedical subjects

C Lafuma

Publications and source records attributed to C Lafuma.

23 records · Page 2Linked to original sources
PubMed1985

Biosynthesis of hyaluronic acid, heparan sulfate and structural glycoproteins in hamster lung explants during elastase induced emphysema.

Hyaluronic acid (HA), heparan sulfate (HS) and structural glycoproteins (SGP) were investigated in explant cultures of hamster lungs by studying incorporation of 14C-glucosamine (14C GlcN) on the first and on the 24th day after intratracheal administration of pancreatic elastase. The different 14C radiolabeled macromolecules were extracted sequentially by 0.4 M guanidinium chloride (0.4 M GUA), 4 M GUA and collagenase digestion. At one day following elastase injury, a 4.2 fold increase of 14C GlcN incorporation into HA released in 0.4 M GUA extract and a 2.6 fold increase into HS released in the collagenase digests were observed compared to control tissues; at 24 days, the increased 14C GlcN incorporation into HA and HS persist but to a lesser extent. Polyacrylamide gel electrophoresis and isoelectric focusing carried out on 4 M GUA extracts, demonstrated identical quantitative and qualitative distribution of 14C GlcN between the major SGP (140 and 110 K with pI 7.8 and 4.5 respectively) in the normal and the experimental groups. These results indicate that pulmonary SGP biosynthesis is not modified at one and 24 days after elastase injury, whereas HA and HS biosynthesis are consistently increased. These results suggest a specific role of these macromolecules in emphysematous injury of the lung.

Animals↗
PubMedDate not supplied

In vitro infection of macrophages by HIV: correlation with cellular activation, synthesis of tumour necrosis factor alpha and proteolytic activity.

Macrophages were obtained after differentiation of healthy donor monocytes. Seven to 9 days after isolation, cells were infected with HIV1. Tumour necrosis factor alpha (TNF alpha) biological activity, TNF alpha- and 1-6-fructose-diphosphatase-gene expression and gelatinase activity were sequentially determined and correlated with viral infection and replication. TNF alpha was only detectable when mature viral particles were isolated in cell culture supernatants; 1-6-fructose diphosphatase mRNA was hyperexpressed in infected cells and its proteolytic activity was tremendously decreased during the early days postinfection. These results would seem to indicate that in human macrophage activation, cytokine secretion and microbicidal proteolytic activity are strongly modified by HIV infection.

Blotting, Northern↗
PubMedDate not supplied

Expression of elastase activity by human monocyte-macrophages is modulated by cellular cholesterol content, inflammatory mediators, and phorbol myristate acetate.

We investigated the effects of a number of stimulatory agents on the production of both cell-associated and extracellular elastase-type enzymes on human monocyte-macrophages in vitro and of the modulation of such effects by modification of cellular cholesterol content. The stimulatory agents included phorbol myristate acetate (PMA) and the inflammatory mediators, lipopolysaccharide (LPS), opsonized zymosan (OZ), and platelet activating factor (PAF). Using the synthetic substrate, N-succinyl-trialanyl-paranitroanilide (SANA), we detected cell-associated elastase-like activity in monocyte-derived macrophages. Such activity increased markedly with cell maturation over the period from 5 to 15 days of adherence culture. While PAF (10 micrograms/ml) and LPS (10 micrograms/ml) were without effect on cell-associated elastase-like activity in macrophages, PMA (100 ng/ml) and OZ (1 mg/ml) markedly stimulated such activity in cells cultured for 15 days. Furthermore, a fivefold increase in the cell-associated elastase-like activity of macrophages occurred upon cholesterol loading of the cells with acetylated low density lipoprotein (AcLDL). By contrast, this activity was markedly diminished upon depletion of cellular cholesterol content after incubation with high density lipoprotein (HDL3). Latent elastinolytic activity in the culture medium was detected by use of a radioactive substrate, insoluble 3H-elastin, after initial tryptic treatment of the medium. Such latent elastase activity was secreted only by activated macrophages; the relative potency of stimulation was: PMA greater than LPS = PAF greater than OZ. Increase in cellular cholesterol content alone markedly enhanced the secretion of elastase (from undetectable levels to 28 ng of 3H-elastin degraded/hr/micrograms DNA). In all cases, both the cell-associated and secreted latent elastinolytic activities were due to metalloproteases, in view of their 90% inhibition by 2 mM EDTA. Cholesterol-loaded macrophages, which displayed an approximately 40-fold increase in total cholesterol content as compared to control cells, remained sensitive to the action of activators of OZ and PMA, while LPS and PAF exerted only weak effects. Our data indicate that cellular cholesterol content and inflammatory mediators are effective stimulants of the production and secretion of elastase-type enzymes by human monocyte-macrophages. Among these factors, cellular cholesterol content, OZ, PAF, and LPS may represent factors of relevance to the inflammatory role of the macrophage in atherogenesis and more specifically to the alteration of elastin structure in the extracellular matrix of the vessel wall.

Cells, Cultured↗
PubMedDate not supplied

Correlation between lung structure and respiratory function in hamsters with experimental emphysema.

The correlation between lung structure and respiratory function was studied in normal hamsters and hamsters with elastase-induced emphysema. Four physiological parameters related to the elasticity of the respiratory system were determined from the quasi-static deflation pressure-volume curve: the shape constant (K) of the mono-exponential model fitted to the curve, the inflated volume (VI) taken as the volume change from a tracheal pressure of 0 to 30 cmH2O, the total respiratory compliance (C), determined near the relaxation volume and the normalized compliance (C/VI). The lung structure was morphologically described by the mean alveolar linear intercept (Lm) and the internal surface area (ISA). The correlations between these indices showed that 1) the four physiological parameters correlate better with Lm than with ISA, and 2) a simple index such as the normalized compliance allows to predict the severity of emphysema satisfactorily (r = 0.85; p less than 10(-6)).

Animals↗