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Biomedical subjects

F Gervais

Publications and source records attributed to F Gervais.

At least 37 records · Page 2Linked to original sources
PubMed1993

Splenic macrophage activation and functions in amyloid enhancing factor-induced secondary amyloidosis. Study of phagocytosis, killing, respiratory burst, and MHC class II surface expression.

Secondary amyloidosis is a systemic disease characterized by the extracellular tissue deposition of insoluble fibrillar amyloid A protein. Aberrant metabolism of serum amyloid A protein by reticuloendothelial cells is thought to result in the accumulation of fibrils within the tissue. Treatment of mice with amyloid-enhancing factor (AEF) in conjunction with an inflammatory stimulus (i.e., AgNO3) induced amyloid deposition within 48-72 h. The activation state of a macrophage largely defines its enzymatic capabilities. In the studies reported here, we examined the effect of AEF on spleen macrophage activation using both functional and phenotypic assays. We found that while AEF in the presence or absence of AgNO3 has no apparent effect on the ability of spleen and liver macrophages to phagocytose or kill Listeria monocytogenes, it appears to block enhanced respiratory burst function (as measured by O2- production) observed with AgNO3 alone. AEF therefore seems capable of inhibiting certain macrophage activation-associated functions while not affecting others. Our activation phenotype studies, using surface Ia expression, reveal that AEF blocks the increase in number of splenic macrophages expressing Ia seen with AgNO3 alone. Treatment with interferon-gamma was found to restore decreased Ia expression in animals given AEF+AgNO3 but did not prevent amyloid A fibril deposition.

Amyloid↗
PubMed1993

The magnitude of macrophage inflammatory response does not directly depend on ability of bone marrow cells to respond to interleukin-3 in mice of different strains.

The multicolony stimulating factor Interleukin-3 (IL-3) has a role in regulating the proliferation, differentiation, and survival of myeloid stem cells and committed progenitor cells within each of the myeloid lineages. It has been referred to as an emergency factor appearing following triggering of an inflammatory response. The ability of bone marrow (BM) stem cells to respond to a stimulus such as IL-3 in vitro may reflect the in vivo capacity of BM stem cells to generate newly BM-derived macrophages being recruited to an inflammatory site. Both parameters, namely the BM cell response to in vitro IL-3 treatment and the magnitude of the macrophage inflammatory response vary among inbred mouse strains. Mice of the A/J strain are known to have weak macrophage inflammatory response to a phlogistic agent and their BM cells are hyporesponsive to IL-3 exposure. In contrast, mice of the C57BL/6 strain mount a high macrophage inflammatory reaction to a stimulus, and their BM cells strongly proliferate in response to the presence of IL-3. Thus, we examined whether or not the type of BM cell response to IL-3 (i.e., A/J- or C57BL/6-like) determines the magnitude of the macrophage inflammatory response using the A x B/B x A recombinant inbred (RI) mouse strain system. The two traits were found not to cosegregate, suggesting that they are not linked. The continuous strain distribution pattern of the magnitude of the macrophage inflammatory response obtained in mice of the A x B/B x A RI strains implies that this trait is under the control of several genes.

Animals↗
PubMed1993

Bone marrow cell response following induction of acute inflammation in different strains of mice.

The magnitude of the macrophage inflammatory response differs among inbred mouse strains. Mice of the A/J strain respond poorly to sterile inflammatory stimuli while those of the C57BL/6 strain show a strong response. Inflammatory macrophages found at the site of inflammation are the product of bone marrow (BM) myeloid stem cells. Mice of the A/J strain were found to have half the number of BM nucleated cells per femur than those of the C57BL/6 strain. The lower BM cellularity may be one reason for the poor macrophage inflammatory response observed in A/J mouse strain. Using A x B/B x A recombinant inbred mouse strains, we determined that the number of nucleated cells per femur found in normal mice was not a determining factor of the magnitude of the macrophage inflammatory response. One additional explanation for the poor macrophage inflammatory response in mice of the A/J strain is their deficiency in the C5 component of complement. Using a C5-sufficient A/J.C5 congenic strain, we have previously shown that the presence of C5 on the A/J background improved their inflammatory response. We compared A/J and A/J.C5 mouse strains to determine whether or not C5 had an impact on the BM cell response to inflammatory stimulus. The presence of C5 on the A/J background could contribute to the improvement of the inflammatory response in mice of the A/J.C5 strain by inducing a greater number of nucleated cells to exit the BM compartment early following induction of inflammation.

Animals↗
PubMed1990

A deficiency of axonal regeneration in C57BL/6J mice.

Axonal regeneration within peripheral nerves and dorsal spinal roots was investigated in inbred strains of mice with known differences in macrophage recruitment and inflammatory functions. During the second week after sciatic nerve crush, counts of regenerating newly myelinated fibres were significantly lower in C57BL/6J mice than in 4 other strains. After dorsal root crush with or without concomitant sciatic nerve transection to enhance regeneration, fibre counts in roots of C57BL/6J were one-fifth of those in A/J mice. Axonal regeneration is subnormal in C57BL/6J mice but this defect appears not to be linked to known deficiencies in macrophage function.

Animals↗
PubMed1990

Killing of Mycobacterium smegmatis by macrophages from genetically susceptible and resistant mice.

The bactericidal function of macrophages was investigated in congenic mice expressing the phenotype of susceptibility (B10.A, Bcgs) or resistance (B10.ABcgr) to mycobacterial infection. When splenic and peritoneal macrophages from these two mouse strains were infected in vitro with Mycobacterium smegmatis, the Bcgr macrophages were shown to inactivate M. smegmatis more efficiently than their Bcgs congenic counterparts. The mechanisms of this superior antimycobacterial activity was studied further. Addition of catalase did not abolish killing to a significant degree in either allelic type of macrophage, suggesting that hydrogen peroxide production was not involved in the killing activity controlled by the Bcg gene. Activation of Bcgs macrophages by exposure to crude lymphokines rendered them equally as efficient as their Bcgr counterparts in their capacity to destroy M. smegmatis. This finding suggests that both the genetically resistant and susceptible macrophages have the potential to kill M. smegmatis in vitro. This potential is expressed constitutively by the Bcgr but not Bcgs macrophages and can be induced, by lymphokine treatment, in the Bcgs macrophages. In a final set of experiments, the macrophage killing of M. smegmatis was evaluated as a test system to type for the Bcg gene allelic type in vitro, using a set of AXB and BXA recombinant inbred strains of mice. Results obtained show that typing of AXB/BXA recombinant inbred strains for the trait of bactericidal activity vs. M. smegmatis in vitro revealed a perfect match with the strain distribution pattern of resistance/susceptibility to Mycobacterium bovis BCG in vivo.

Animals↗
PubMed1990

apo-SAA1/apo-SAA2 isotype ratios during casein- and amyloid-enhancing-factor-induced secondary amyloidosis in A/J and C57BL/6J mice mice.

A/J mice are resistant while C57BL/6J are susceptible to casein-induced secondary amyloidosis. One mechanism responsible for this phenotypic expression of resistance/susceptibility was shown to operate at the level of production of the 'amyloid-enhancing factor' (AEF). AEF and processing of the apo-SAA protein appear almost concomitantly during amyloidogenesis. In order to determine if AEF played a role in the processing of the apo-SAA protein, three major parameters (apo-SAA1/apo-SAA2 ratios, level of AEF, and fibril formation) were determined during casein-induced secondary amyloidosis. Kinetics of AEF production and serum levels of the two major apo-SAA isotypes were compared in A/J and C57BL/6J animals. Both strains showed equal relative amounts of the two isotypes after seven, 15 and 21 casein injections, irrespective of the fact that the A/J strain had no detectable level of AEF and no amyloid deposition; while C57BL/6J mice had a high AEF level and were amyloidotic after 15 and 21 injections. An increased apo-SAA1/apo-SAA2 ratio due to a decrease in apo-SAA2 was noted after 38 days of casein injections when both strains had extensive deposits of amyloid fibrils. Involvement of AEF as an effector molecule was determined by following the ratio of the two major serum apo-SAA isotypes and fibril formation during an accelerated protocol of amyloid induction in C57BL/6J animals. AEF had no direct effect on apo-SAA isotype ratios in the serum.

Amyloidosis↗
PubMed1990

Effect of drug additives to peritoneal dialysis solutions on the viability and function of mouse peritoneal cells.

Peritoneal dialysis (PD) solutions and therapeutic drugs frequently added to PD solutions in clinical practice have been shown to reduce the viability and to impair the function of mouse peritoneal cells. The cytotoxicity of PD solutions, directly related to the dextrose concentration, was more marked towards resident than elicited peritoneal cells. None of the drug additives, heparin and insulin amongst them, were cytotoxic when tested alone or combined with 4.25% PD solution, with the exception of phosphatidylcholine which markedly enhanced the cytotoxicity of the PD solution. While the function of mouse peritoneal macrophages as measured by their hydrogen peroxide production was largely unaffected by PD solutions and drug additives when tested separately, the combination of 4.25% PD solution with any of the drug additives resulted in complete abolition of macrophage respiratory burst. The results should caution against the indiscriminate addition of drugs to PD solutions in dialysis patients.

Animals↗
PubMed1989

The C5-sufficient A/J congenic mouse strain. Inflammatory response and resistance to Listeria monocytogenes.

A/J mouse strain poorly responds to an inflammatory stimulus and is highly susceptible to Listeria monocytogenes (Lm) infection. This defect in the phagocyte inflammatory response caused by the C5 component of C deficiency was shown, by linkage analysis, to be the major reason for the extreme susceptibility of A/J mice to Lm infection. The importance of this genetic defect in C5 in relation to the poor macrophage inflammatory response and to the susceptibility to Lm infection was evaluated by developing a C5-sufficient congenic A/J mouse strain. This A/J.C5 mouse strain was studied for its inflammatory response and for its susceptibility to Lm infection. C5-sufficient congenic A/J.C5 mice showed a slight improvement (2X) in their level of macrophage inflammatory response; however, they did not mount an as strong response as the Listeria-resistant C57BL/6J mice which donated the C5 allele. When infected with Lm, A/J.C5 mice were found to be as resistant as C57BL/6J mice. These results suggest that the presence of C5 on an A/J background partially improves the deficient macrophage inflammatory response of that strain. This increase is sufficient to render the A/J.C5 mouse strain highly resistant to Listeria infection. A/J.C5 mouse strain represents a new tool for the study of the importance of C5 in resistance to infection and in the regulation of the macrophage inflammatory response.

Animals↗
PubMed1989

Quantitative model of mononuclear phagocyte lineage proliferation in murine bone marrow.

An analysis and a synthesis of published and original experimental evidence have been performed with a view to providing a global qualitative and quantitative description of the proliferation of monocyte precursors in murine bone marrow. Two versions of a mathematical model are proposed. The first consists of two dividing generations of granulocyte-macrophage colony-forming cells (GM-CFC) and two dividing generations of macrophage colony-forming cells (M-CFC), differentiating into promonocytes (PM) and then into monocytes (MC). The second version consists of two generations of GM-CFC and three generations of M-CFC, followed by PM and MC. Both are compatible with experimental data, and further evidence is needed to elaborate a unique representation. The kinetic constants have been taken from published material whenever possible and estimated from available data and model kinetics in the case of unknown quantities. The models are applied to a pulse labeling assay, and calculated labeled subpopulations are compared with experimental values. Agreement is satisfactory for both versions in the case of MC, while a calculated PM labeling index falls more rapidly than the experimental values. However, inconsistency also exists between PM and MC experimental data.

Animals↗
PubMed1989

Susceptibility to a mouse acquired immunodeficiency syndrome is influenced by the H-2.

The development of a mouse acquired immunodeficiency syndrome (MAIDS) induced following LP-BM5 MuLV infection depends on host genetic factors. Susceptible mice, such as C57BL/6J mice, develop a profound impairment of lymphoproliferative response to mitogens and hyperplasia of lymphoid organs and succumb to infection within 6 months. These changes do not occur in resistant mice, such as A/J mice. Resistance to MAIDS is a dominant trait since (C57BL/6J x A/J)F1 hybrid mice did not develop any immune dysfunctions following infection. Genetic regulation of the trait of resistance/susceptibility to MAIDS was determined in AXB/BXA recombinant inbred (RI) mouse strains (derived from resistant A/J and susceptible C57BL/6J progenitors). Two different criteria were used to determine their resistance or susceptibility to developing MAIDS: the gross pathologic evaluation of lymphoid organs at 13-15 weeks of infection, and survival. RI mouse strains segregated into two non-overlapping groups. The first group did not develop any significant pathology, and these mouse strains were considered as resistant to MAIDS. The second group showed the virus-induced pathological changes as well as an immunological dysfunction as seen in C57BL/6J progenitor mice, and these strains were thus considered as susceptible to MAIDS. This bimodal strain distribution pattern of resistance/susceptibility to MAIDS among the RI strains suggests that this phenotype is controlled by a single gene. Linkage analysis with other allelic markers showed a strong association between resistance/susceptibility to MAIDS and the H-2 complex. Possession of the H-2b haplotype derived from C57BL/6J mice was associated with susceptibility to MAIDS, while the H-2a haplotype conferred resistance to the disease. This finding was confirmed by demonstrating that H-2a congenics on the susceptible C57BL/10 background were as resistant to MAIDS as A/J mice which donated the H-2a locus. Gene(s) within the H-2 complex thus represent the major regulatory mechanism of resistance/susceptibility to MAIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1989

The influence of dietary whey protein on tissue glutathione and the diseases of aging.

This study compared the effects of a whey-rich diet (20 g/100 g diet), with that of Purina mouse chow or casein-rich diet (20 g/100 g diet), on the liver and heart glutathione content and on the survival of old male C57BL/6NIA mice. The study was performed during a limited observation period of 6.3 months. In mice fed the whey protein-rich diet between 17 months and 20 months of age, the heart tissue and liver tissue glutathione content were enhanced significantly above the corresponding values of the casein diet-fed and Purina-fed mice. Mice fed the whey protein diet at the onset of senescence at 84 weeks, exhibited increased longevity as compared to mice fed Purina mouse chow over the 6.3 month observation period extending from the age of 21 months (corresponding to a human age of 55 years) to 26-27 months of age (corresponding to a human age of 80 years), during which time 55% mortality was observed. The corresponding mean survival time of mice fed the defined casein diet is almost identical to that of Purina-fed controls. Body weight curves were similar in all three dietary groups. Hence a whey protein diet appears to enhance the liver and heart glutathione concentration in aging mice and to increase longevity over a 6.3 month observation period.

Aging↗
PubMed1988

Amyloid-enhancing factor: production and response in amyloidosis-susceptible and -resistant mouse strains.

Genetic variations in the development of casein-induced amyloidosis exist among inbred strains of mice: CBA/J and C57BL/6J mice are susceptible, while A/J strain mice are resistant to this disease. Amyloidosis is usually induced by daily injections of an inflammatory stimulus for 2-3 wk. The deposition of amyloid in experimental animals can be accelerated by injection of a material called amyloid-enhancing factor (AEF); when injected concomitantly with an inflammatory stimulus, AEF provokes appearance of amyloidosis as early as 2 days after injection. AEF is extracted from amyloid laden or from normal organs (although in small amount). Our studies were designed to determine if the resistance to amyloidosis seen in A/J mice was either due to a lack of AEF production or to an inability of these mice to respond to AEF. A standard source of CBA/J-derived AEF facilitated the development of amyloidosis in the organs of both the susceptible (CBA/J, C57BL/6J) and the resistant A/J mice. On the contrary, amyloidosis was only induced in susceptible CBA/J hosts when material derived from susceptible (CBA/J, C57BL/6J) animals was injected. CBA/J mice injected with A/J-derived AEF preparation did not develop amyloidosis. These results thus suggest that the determination of resistance or susceptibility to secondary amyloidosis could operate at the level of AEF production.

Amyloidosis↗