A lymphokine distinct from interferon-gamma that activates human monocytes to kill Leishmania donovani in vitro.
Human interferon-gamma (IFN-gamma), a T cell lymphokine (LK), activates monocytes to kill many intra- and extracellular pathogens. In fact, previous reports assert that all activity in LK for macrophage activation is due to IFN-gamma. To test this assertion, we examined monocyte interactions with amastigotes of Leishmania donovani after treatment with recombinant DNA or affinity-purified leukocyte IFN-gamma and IFN-gamma containing LK. Cells treated with at least 200 IU/ml IFN-gamma were microbicidal for L. donovani. Analysis of IFN-gamma dose responses for induction of microbicidal activity by recombinant IFN-gamma (r-IFN-gamma) and LK, however, documented a striking difference: LK was 25-fold more efficient than r-IFN-gamma at equivalent IFN-gamma titers. This large difference suggested that monocyte activation factor(s) in LK may not be IFN-gamma. Rabbit anti-IFN-gamma completely inhibited antiviral activity in LK but did not abrogate the ability to induce monocyte cytotoxicity against leishmania. Furthermore, removal of IFN-gamma from LK by monoclonal anti-IFN-gamma affinity chromatography or by treatment with anti-IFN-gamma followed by staphylococcal protein A chromatography also did not inhibit LK activity. Fractionation of LK on Sephadex G-100 revealed two activity peaks: one in the 50,000 to 60,000 m.w. range coincident with IFN-gamma, and the other at 25,000 to 30,000 daltons with no IFN-gamma. These studies document LK physicochemically and antigenically distinct from IFN-gamma that activate monocytes to kill L. donovani. Such novel factors may have broad import for the study of macrophage-mediated host defenses and for development of immunotherapeutic regimens.
Hoover
D L
DL
Finbloom
D S
DS
Crawford
R M
RM
Nacy
C A
CA
Gilbreath
M
M
Meltzer
M S
MS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology; D001667:Binding, Competitive; D006224:Cricetinae; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007371:Interferon-gamma / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D007893:Leishmania donovani / Q000254:growth & development / Q000276:immunology*; D008222:Lymphokines / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D016215:Macrophage-Activating Factors; D008970:Molecular Weight; D009000:Monocytes / Q000276:immunology* / Q000382:microbiology; D011817:Rabbits
D000911:Antibodies, Monoclonal; D007106:Immune Sera; D008222:Lymphokines; D016215:Macrophage-Activating Factors; D007371:Interferon-gamma