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Biomedical subjects

A C Allison

Publications and source records attributed to A C Allison.

At least 199 records · Page 11Linked to original sources
PubMed1977

Macrophage responses to mouldy hay dust, Micropolyspora faeni and zymosan, activators of complement by the alternative pathway.

Mouse peritoneal macrophages in culture exposed to mouldy hay dust, Micropolyspora faeni or glycopeptide or protein/glycoprotein fractions from this organism show marked biochemical changes. For comparison the interaction of cultured macrophages with zymosan has been investigated. All these agents induce the release of hydrolytic enzymes from macrophages, even in the absence of serum in the medium. The release is time- and dose-dependent and is not associated with loss of the cytoplasmic enzyme lactate dehydrogenase or any other sign of cell death. The parallelism between the capacity of these agents to activate the complement system via the alternative pathway and to induce inflammatory responses in vivo and selective lysosomal enzyme secretion from cultures of macrophages is discussed. The in vitro phenomena seen with mouldy hay dust, M. faeni, the protein/glycoprotein and the glycopeptide derived from it, may be relevant to understanding the role of mononuclear phagocytes in the disease farmer's lung and other inflammatory reactions.

Animals↗
PubMed1977

The selective release of lysosomal acid hydrolases from mouse peritoneal macrophages by stimuli of chronic inflammation.

The paralelism between the capacity of various agents to elicit chronic inflammatory responses in vivo and to induce the selective release of lysosomal enzymes from cultures of mouse peritoneal macrophages in vitro is discussed. Zymosan elicits an intense inflammatory response when injected i.m. in mice. Chrysotile asbestos produces a response of a similar nature and intensity as is seen with zymosan, while injections of acid-leached asbestos and polystyrene latex are not followed by inflammation. It is also shown that zymosan and asbestos induce a dose-dependent increase in the total enzyme activity of an inflamed muscle. On the other hand latex and acid-leached asbestos caused no significant increases in lysosomal enzyme levels. Agents eliciting inflammatory responses, such as zymosan and chrysotile asbestos induce a selective release of acid hydrolases from cultured macrophages; in contrast agents lacking the capacity to induce inflammation, such as latex and acid-leached chrysotile asbestos, do not induce the release of lysosomal enzymes from cultured macrophages.

Animals↗
PubMed1976

Correlation of persistent mouse hepatitis virus (MHV-3) infection with its effect on mouse macrophage cultures.

MHV 3 has three distinct effects in different strains of mice: strain A mice are completely resistant, most strains (including C57BL, DBA/2, BALB/c and NZB strains) die of acute hepatitis whereas in certain strains (eg. C3H and A2G) the virus produces a persistent infection with neurological symptoms. In cultures of peritoneal macrophages from susceptible strains, MHV-3 replicated freely, with giant cell formation. No replication was observed in macrophages from strain A mice. In contrast to this full susceptibility or resistance, macrophage cultures from strains of mice in which persistent infections occur showed an intermediate susceptibility, as judged by the intensity of the cytopathic effect, the presence of viral antigens in the cytoplasm and levels of viral replication. Possible ways in which the intermediate susceptibility of macrophages and persistent infections might be related are discussed.

Animals↗
PubMed1976

The macrophage as a secretory cell in chronic inflammation.

Although it is clear that macrophages are always present at sites of chronic inflammation their contribution to the evolution of these lesions is not well understood. In vitro studies have shown that macrophages secrete a variety of products on exposure to different stimuli. These include hydrolytic enzymes, active at acid or neutral pH, with known capacity for degrading tissue constituents. Lysosomal acid hydrolases are released from viable cells over a prolonged period of time by various agents known to cause, or are associated with, chronic inflammation. These agents may be nonimmunogenic substances, such as carrageenan and asbestos, which interact directly with macrophages or alternatively the products of immune reactions involving either B or T lymphocytes. These lymphocyte products include immune complexes of certain composition and the secreted products of T lymphocytes stimulated by nonspecific mitogens or specific antigens. In marked contrast biologically inactive substances such as latex particles or digestible substrates such as erythrocytes do not induce the selective release of acid hydrolases from macrophages. It is clear that alghough macrophages secrete abundant amounts of neutral proteinases under certain conditions this release does not occur necessarily during the release of acid hydrolases induced by inflammatory agents. The role played by acid and neutral hydrolases secreted by macrophages during the various stages of chronic inflammatory responses remains to be clarified.

Animals↗
PubMed1976

Cytolytic effects of the complement cleavage product, C3a.

Purified C3a, a cleavage product of the third component of complement,was incubated with various cell types of human and mouse origin. All the tumour cell types tested were lysed by low concentrations of C3a, whereas normal human lymphocytes were relatively resistant. No lysis was produced by C3 or C3b. The possible role of C3a in immunity against tumours is discussed.

Animals↗
PubMed1976

Nature of the effector cells responsible for antibody-dependent cell-mediated killing of Cryptococcus neoformans.

Studies were performed to identify the types of human peripheral blood leukocytes capable of killing Cryptococcus neoformans in the presence of anticryptococcal antibody in vitro. A total of 24.1 +/- 2.7% (mean +/- standard error of the mean of four experiments) of the original cryptococcal inoculum survived in a mixed mononuclear, cell preparation (approximately 30% monocytes) after 4 h of incubation at 37 degrees C with rabbit anticryptococcal antibody. When phagocytic cells were removed, there was 36.4 +/- 4.6% survival in six experiments, compared with 52.8% survival in the presence of purified granulocytes (mean of two experiments) and 96.9 +/- 1% survival in the presence of purified T cells. There was never any significant killing in control mixtures that contained leukocytes with normal rabbit serum nor in those that contained anticryptococcal antibody without effector leukocytes. Significant antibody-dependent fungicidal activity was seen with ratios of effector to target cells as low as 6.25:1. These observations indicate that multiple types of peripheral blood leukocytes, excluding T cells, are capable of antibody-dependent fungicidal activity.

Antibodies, Fungal↗
PubMed1976

Role of adenosine deaminase in lymphocyte proliferation.

Activity of adenosine deaminase (ADA), an enzyme known to be deficient in some patients with severe combined immunodeficiency, increased three-fold within a 24-hour exposure of human peripheral blood lymphocytes to phytohaemagglutinin (PHA) in culture. This increase took place before the onset of DNA synthesis. Increased levels of ADA activity were also observed in lymphocytes incubated with pokeweed mitogen (PWM) for 60 hr. DNA synthesis induced by PHA, PWM or mixed lymphocyte cultures (MLC) was strongly inhibited by adenosine at concentrations of 10(-4) M or higher when human peripheral blood lymphocytes were cultured in a medium supplemented with horse serum, which lacks ADA. 10(-6)-10(-8) M coformycin, a potent inhibitor of ADA, inhibited PHA-, PWM- and MLC-induced DNA synthesis to a variable extent, whereas thymidine incorporation induced by Salmonella lipopolysaccharide (LPS) in mouse spleen cell cultures was strongly inhibited (by 75% or more) by 10(-6) M coformycin. Combination of 10(-7)-10(-8) M coformycin and 10(-4)-10(-5) M adenosine synergistically inhibited mitogen- or MLC-induced DNA synthesis in human and mouse lymphocyte cultures. These results, together with observations on children with ADA deficiency, provide evidence that adenosine deaminase is highly important for lymphocyte proliferation. Human peripheral blood lymphocytes incubated with PHA, 10(-5) M adenosine and 10(-7) M coformycin showed some cytotoxicity whereas the rate of 51Cr release from normal lymphocytes was not modified by the drugs. These findings suggest that in vivo clones of lymphocytes responding to specific antigens might be eliminated by coformycin, which may prove to be useful as a specific immunosuppressive agent.

Adenosine↗