Leukocyte antimicrobial function in patients with leprosy.

Drutz, David J.; Cline, Martin J.; Levy, Louis

doi:10.1172/jci107570

Cited by 30 publications

(13 citation statements)

References 26 publications

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“…This hypothesis does not exclude the possibility that mononuclear phagocytes located at the site of infection are somehow inhibited from being activated. Drutz et al (19) previously reported that nonactivated human monocytes from patients with iepromatous and tuberculoid leprosy have comparable capacities to kill a variety of microorganisms (19) Although mononuclear phatocytes must generally be activated to control infection by intracellular pathogens, this study by Drutz et al further supports the hypothesis that circulating mononuclear phagocytes from patients with lepromatous leprosy have a normal antimicrobial capacity.…”

Section: Discussionsupporting

confidence: 74%

Defective production of monocyte-activating cytokines in lepromatous leprosy.

Horwitz¹,

Levis²,

Cohn³

1984

The Journal of Experimental Medicine

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We have examined the capacity of monocytes from patients with leprosy to undergo activation and the capacity of mononuclear cells from these patients to incorporate [3H]thymidine and produce monocyte-activating cytokines. Monocytes from patients with either lepromatous or tuberculoid leprosy were activated by concanavalin A (Con A)-induced mononuclear cell supernatants generated from the leukocytes of a normal person. Monocytes activated by these supernatants strongly inhibited L. pneumophila multiplication, and the degree of inhibition was comparable in both groups of patients. Mononuclear cells from patients with either form of leprosy responded comparably to Con A with vigorous [3H]thymidine incorporation. Mononuclear cells from patients with tuberculoid leprosy also vigorously incorporated [3H]thymidine in response to M. leprae antigens. In contrast, mononuclear cells from patients with lepromatous leprosy did not exhibit significant [3H]thymidine incorporation in response to M. leprae antigens. The capacity of mononuclear cells to generate monocyte-activating cytokines generally paralleled their capacity to incorporate [3H]thymidine in response to Con A and M. leprae. Mononuclear cells from patients with either form of leprosy responded to Con A with the production of cytokines (supernatants) able to activate normal monocytes, expressed by inhibition of L. pneumophila multiplication. However Con A-induced supernatants from patients with lepromatous leprosy were less potent than Con A-induced supernatants from patients with tuberculoid leprosy. Mononuclear cells from patients with tuberculoid leprosy responded to M. leprae antigens with the production of potent monocyte-activating supernatants. In contrast, mononuclear cells from patients with lepromatous leprosy did not produce monocyte-activating cytokines in response to M. leprae antigens. These studies support the hypothesis that the immunological defect in lepromatous leprosy results from a failure to activate mononuclear phagocytes rather than from an intrinsic inability of these cells to be activated. We suggest that the failure to activate mononuclear phagocytes stems from defective production of monocyte-activating cytokines in response to M. leprae antigens.

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Section: Discussionsupporting

confidence: 74%

Defective production of monocyte-activating cytokines in lepromatous leprosy.

Horwitz¹,

Levis²,

Cohn³

1984

The Journal of Experimental Medicine

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“…T H E histological classification of leprosy has been well worked out (Ridley 1974) and correlated with lymphocytic transformation test (LTT) results with circulating lymphocytes (Myrvang et al, 1973;Bjune et al, 1976;Job et al, 1976). Circulating lymphocytes have been further studied by rosette tests (Dwyer, Bullock and Fields, 1973;Nath et al, 1974;Lim et al, 1974;Sher et al, 1976) and the performance of macrophages from leprosy patients in vitro has been shown to be dependent on the presence of lymphocytes by Godal et al (1971), Drutz, Cline and Levy (1974) and Parmaswaran et al (1976). However, identification of cells by surface markers has not so far been applied to cells present in leprosy lesions.…”

mentioning

confidence: 99%

Surface markers on lymphocytes and cells of the mononuclear phagocyte series in skin sections in leprosy

Ridley

Turk

1978

The Journal of Pathology

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E, EA and EAC rosetting techniques and Ig fluorescence were used in a study of receptor sites in cryostat sections of lesions through the spectrum of leprosy, and for comparison in some other mycobacterial and granulomatous lesions. Anti-C3, and trypsin were used as blocking agents. Lymphocytes in borderline lepromatous leprosy produced EA adherence and IgG fluorescence indicating B type cells. Lymphocytes in tuberculoid leprosy produced neither E or EA adherence and no fluorescence; these cells were presumed to be T cells. EAC and EA adherence was more marked in areas of macrophage infiltration, where there were few lymphocytes, than over the lympocytes themselves. Two distinct patterns emerged: (i) EA binding together with IgG fluorescence was seen in active lepromatous leprosy and could be localised to the surface of individual macrophages, and (ii) EAC binding together with IgM fluorescence was seen in the granuloma of tuberculoid leprosy and sarcoidosis, but could not be definitely related to cell surface; rather it was diffusely spread over the whole granuloma; EAC adherence was diminished by anti-C3 serum. Trypsin removed EA binding completely, but only diminished EAC adherence. It is suggested that the EA pattern indicates immunoglobulin receptors on macrophage and lymphocyte surfaces: and that the EAC binding (which is stronger than EA) involves C3 and IgM receptors at extracellular sites as well as C3 receptor sites on epithelioid cell surfaces. EA and EAC binding were enhanced in borderline tuberculoid leprosy in reaction and erythema nodosum leprosum, suggesting that immunoglobulin and complement receptor sites increase in number with enhanced hypersensitivity.

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“…Thus, macrophage effector function in leprosy has been addressed indirectly. Although there is some evidence that macrophages from LL patients are deficient in their ability to digest M. leprae (12), not all workers have found such deficiencies (52,197). Our own studies showed that mice with potent populations of activated macrophages were markedly resistant to footpad infection with M. Ieprae (120,121).…”

Section: Clin Microbiol Revmentioning

confidence: 81%

“…On the other hand, Nathan et al (165) and Kaplan et al (106) showed not only that monocytes from LL patients were deficient in hydrogen peroxide production (and presumably microbicidal capacity as well), but also that this defect was reversed by treatment with IFN-y. These findings are not consistent with studies that showed no defect in the innate microbicidal capacity towards other pathogens of macrophages from LL patients (52). We have recently demonstrated that activated mouse macrophages have a deleterious, probably microbicidal effect on M. Ieprae as shown by electron microscopy (220) and marked inhibition of adenosine 5'-triphosphate (ATP) content and synthesis of PGL-I (186,224).…”

Section: Clin Microbiol Revmentioning

confidence: 89%