Lipoarabinomannan as a regulator of the monocyte apoptotic response to Mycobacterium bovis BCG Danish strain 1331 infection.
The mannosylated lipoarabinomannan (ManLAM) from mycobacterial species possesses strong immunomodulatory effects. Here we examined the ability of Mycobacterium tuberculosis ManLAM to interfere with the apoptotic response of mouse monocyte cell line, RAW 264.7 infected with Mycobacterium bovis BCG Danish strain. Incubation of BCG-infected monocytes with ManLAM decreased production of NO and the numbers of apoptotic cells which synergized with the polarization of mitochondrial membrane. Activities of caspase-1, -3, -8 and 9 followed pattern of apoptosis suppression by ManLAM, except for caspase-1, which showed no significant change in activity. ManLAM also stabilized anti-apoptotic ratio of bcl-2/bax expression in BCG-infected cells and blocked activation of Fas/FasL-induced pathway of apoptosis. Thus, ManLAM, apart from blocking mitochondrial pathway of apoptosis, may induce several other pathways regulating apoptotic response in BCG-infected mouse monocytes.
Krzyzowska
Małgorzata
M
Division of Immunology, Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw Agricultural University, Poland. krzyzowska@yahoo.com
Schollenberger
Ada
A
Pawłowski
Andrzej
A
Hamasur
Beston
B
Winnicka
Anna
A
Augustynowicz-Kopeć
Ewa
E
Niemiałtowski
Marek
M
D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000032:analysis; D002460:Cell Line; D005786:Gene Expression Regulation; D008070:Lipopolysaccharides / Q000276:immunology*; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D009000:Monocytes / Q000737:chemistry / Q000166:cytology / Q000276:immunology*; D009163:Mycobacterium bovis / Q000276:immunology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494827:Bax protein, mouse; D008070:Lipopolysaccharides; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C050016:lipoarabinomannan; D009569:Nitric Oxide; D020169:Caspases