Ineffective elimination of Leishmania major by inflammatory (MRP14-positive) subtype of monocytic cells.

Abstract

Myeloid-related protein (MRP) 14, an intracellular protein involved in calcium-dependent activation of myeloid cells, presents a differentiation marker for a subtype of macrophages. In experimental leishmaniasis, BALB/c mice succumb to visceral dissemination after infection with L. major, due to a Th2 cell response, while C57Bl/6 mice develop protective immunity associated with a Th1 cell response. We have previously shown that resistance in (C57Bl/6 mice was also associated with a significantly lower percentage of MRP14-positive cells in the infiltrate than in susceptible BALB/c mice. In C57Bl/6 mice, weekly injections of bone marrow (BM) cells enriched with MRP14-positive cells (d1 of culture) did not reverse, but prolonged the course of infection, associated with increased local parasite spread. In BALB/c mice a single dose of an antiphlogistic agent (dexamethasone or lipoxygenase inhibitor) was associated with reduction of infiltrating MRP14-positive cells and also with a decrease of parasite loads in footpads, lymph nodes as well as spleens, and with delayed progression of disease, Double labeling experiments in vitro revealed that at least 43.1% of MRP14-positive mononuclear cells in BM cultures (8h) had phagocytosed parasites after 4 h of co-incubation. Activation by IFN-gamma (20 U/ml) for 24h and 48h did not significantly reduce parasite load in these cells. In contrast, 77.0% of F4/80-positive macrophages (6d of culture) were infected with L. major parasites and these cells responded to activation with IFN-gamma (20 U/ml) with significant reduction of parasite load (25.3%). The protein MRP14 did not have an effect on parasite survival in vitro. Thus, the impaired capability of MRP14-positive cells to kill L. major upon stimulation may be one reason for the adverse course of infection observed with their increased appearance.

• Authors: K Steinbrink, F Schönlau, U Rescher, U Henseleit, T Vogel, C Sorg, C Sunderkötter
• Journal: Immunobiology (Immunobiology) Vol. 202 Issue 5 Pg. 442-59 (Nov 2000) ISSN: 0171-2985 [Print] Netherlands
• PMID: 11205374 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Antigens, Differentiation
• Calgranulin B
• Quinolines
• S100 Proteins
• monocyte-macrophage differentiation antigen
• 2-(4-(quinolin-2-yl-methoxy)phenyl)-2-cyclopentylacetic acid
• Dexamethasone
• Interferon-gamma

Topics

• Animals
• Anti-Inflammatory Agents (administration & dosage)
• Antigens, Differentiation (analysis, pharmacology)
• Calgranulin B
• Cells, Cultured
• Dexamethasone (administration & dosage)
• Disease Models, Animal
• Female
• Immunohistochemistry
• In Vitro Techniques
• Interferon-gamma (pharmacology)
• Leishmania major (drug effects, pathogenicity)
• Leishmaniasis, Cutaneous (drug therapy, immunology, parasitology)
• Lymph Nodes (parasitology)
• Macrophages (immunology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Microscopy, Fluorescence
• Monocytes (immunology)
• Phagocytosis
• Quinolines (administration & dosage)
• S100 Proteins (analysis, pharmacology)
• Spleen (parasitology)