The Enhancement of Macrophage Bacteriostasis by Products of Activated Lymphocytes

Fowles, Robert E.; Fajardo, Ileana; Leibowitch, Jacques; David, John R.

doi:10.1084/jem.138.4.952

Cited by 201 publications

(75 citation statements)

References 22 publications

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“…Normal lymph node cells stimulated with a mitogen such as PHA or Con A conferred weak but definite bactericidal activity against tubercle bacilli on normal macrophages. These results may be coincident with the results of Fowles and co-workers in which normal lymphoid cells of guinea pigs stimulated with Con A showed only bacteriostatic but not bactericidal effects on L. monocytogenes within cultured macrophages [12]. The relationship between soluble factors produced by sensitized lymphocytes and those produced by normal lymphocytes stimulated with mitogens remains to be elucidated in further studies.…”

Section: Discussionsupporting

confidence: 64%

In Vitro Studies on the Mechanism of Acquired Resistance to Tuberculous Infection

Muraoka

Takeya

Nomoto

1976

Japanese Journal of Microbiology

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Immune lymph node cells were obtained from mice immunized with bovine gamma globulin (BGG) in complete Freund's adjuvant or allogeneic MH 134 tumor cells. They showed the capacity of conferring bactericidal activity on macrophages infected with Mycobacterium tuberculosis, H37Rv, when they were incubated on macrophage monolayers together with the corresponding antigen, i.e., BGG or solubilized cellular antigen of the tumor cells. However, such capacity was lower than that of tubercle bacilli-immune lymph node cells. Culture supernatants were harvested after incubation of tubercle bacilli-immune, BGG-immune or allogeneic tumor-immune lymph node cells with the corresponding antigen for 24 hr. Macrophages were altered so as to suppress intracellular bacillary growth when macrophage monolayers were exposed to the supernatants for more than 2 days. When normal lymph node cells were incubated on normal macrophage monolayers together with a mitogen such as PHA or concanavalin A, growth of tubercle bacilli within the macrophages was slightly but difinitely suppressed. The mechanism of elicitation of cellular immunity to the infection with tubercle bacilli is discussed on the basis of results presented in this and the preceding paper.

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Section: Discussionsupporting

confidence: 64%

In Vitro Studies on the Mechanism of Acquired Resistance to Tuberculous Infection

Muraoka

Takeya

Nomoto

1976

Japanese Journal of Microbiology

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“…Lymphokines produced by sensitized lymphocytes have been shown to confer on animal macrophages or human monocytes enhanced ability to resist or kill M. tuberculosis (44,45), L. monocytogenes (46)(47)(48)(49), Leishmania enrietti (50), T. gondii (51)(52)(53)(54)(55)(56), and Trypanosoma cruzi (57,58). Lymphokine-activated macrophages may play a similar role in eradicating L. pneumophila in vivo.…”

Section: Resultsmentioning

confidence: 99%

Legionnaires' Disease Bacterium (Legionella pneumophila) Multiplies Intracellularly in Human Monocytes

Horwitz¹,

Silverstein²

1980

J. Clin. Invest.

626

524

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A B S T R A C T We have studied the interaction between virulent egg yolk-grown Legionella pneumophila Philadelphia 1 and human blood monocytes in vitro. The leukocytes were cultured in antibiotic-free tissue culture medium supplemented with 15% autologous human serum.L. pneumophila multiplied several logs, as measured by colony-forming units, when incubated with monocytes or mononuclear cells; the mid-log phase doubling time was 2 h. The level to which L. pneumophila multiplied was proportional to the number of mononuclear cells in the culture. L. pneumophila multiplied only in the adherent fraction of the mononuclear cell population indicating that monocytes but not lymphocytes support growth of the bacteria. Peak growth ofL. pneumophila was correlated with destruction of the monocyte monolayer. By fluorescence microscopy using fluorescein conjugated rabbit anti-L. pneumophila antiserum, the number of monocytes containing L. pneumophila increased in parallel with bacterial growth in the culture. At the peak of infection, monocytes were packed full with organisms. By electron microscopy, L. pneumophila in such monocytes were found in membrane-bound cytoplasmic vacuoles studded with structures resembling host cell ribosomes.

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“…Thus, the "apparent Kin", i.e., concentration to achieve only half maximal stimulation, would require a 10-fold concentration of the original lymphocyte supernates. One interpretation of this apparent requirement for a very high concentration of lymphocyte factors is that a cell-to-cell (macrophage-lymphocyte) interaction is required for maximal effects, as suggested by Fowles et al (19) for enhancement of macrophage bacteriostasis, and by Farr et al (29) for the stimulated secretion of mitogenic protein by cultures containing T lymphocytes and macrophages. Though this kind of analysis in complex biological systems should be viewed with caution, the observed results indicate that further investigation of the possibility is warranted.…”

Section: Discussionmentioning

confidence: 99%

Alteration of some functional and metabolic characteristics of resident mouse peritoneal macrophages by lymphocyte mediators.

Lazdins¹,

Kühner²,

David³

et al. 1978

The Journal of Experimental Medicine

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Resident mouse peritoneal macrophages were incubated in Sephadex G-100 fractions of supernates from concanavalin A-stimulated lymphocytes. A significant effect of the lymphocyte supernatant fractions containing mediators on macrophage 5'-nucleotidase, glucose-1 14C oxidation, cell maintenance, and migration is reported. The 5'-nucleotidase was depressed to an extent similar to that seen in activated macrophages obtained from Listeria-infected mice. On the other hand, glucose-1-14C oxidation was enhanced, but not to the same degree as seen in the counterparts in vivo. Whereas migration inhibitory factor (MIF) and cell adherence-augmenting activity were found in a number of adjacent fractions, the metabolic effects were found predominantly in a single fraction. Resident peritoneal macrophages or those elicited by the injection of a lymphocyte-derived chemotactic factor were more responsive with respect to the biochemical changes than caseinate-elicited macrophages. On the other hand, caseinate-elicited macrophages appeared to be more sensitive with respect to the effects of mediator(s) on cell retention. A possible dissociation between MIF and cell-adherence augmenting activity, on the one hand, and the entities that stimulate glucose-1-14C oxidation is reported, based on fractionation studies, and loss of the latter activity upon storage of lymphocyte supernates.

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The Enhancement of Macrophage Bacteriostasis by Products of Activated Lymphocytes

Abstract: A; KRP, Krebs-Ringer phosphate buffer; MEM, minimal essential medium; MEM-S, 15% heat inactivated guinea pig serum; MIF, migration inhibitory factor; OCB-BGG, orthochlorobenzoyl bovine gamma globulin; PEC, peritoneal exudate ceils; PPD, purified protein derivative.

Cited by 201 publications

References 22 publications

In Vitro Studies on the Mechanism of Acquired Resistance to Tuberculous Infection

In Vitro Studies on the Mechanism of Acquired Resistance to Tuberculous Infection

Legionnaires' Disease Bacterium (Legionella pneumophila) Multiplies Intracellularly in Human Monocytes

Alteration of some functional and metabolic characteristics of resident mouse peritoneal macrophages by lymphocyte mediators.

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