Antimicrobial proteins of murine macrophages.
Three murine microbicidal proteins (MUMPs) were purified from cells of the murine macrophage cell line RAW264.7 that had been activated by gamma interferon. Similar proteins were also present in nonactivated RAW264.7 cells, in cells of the murine macrophage cell line J774A.1, and in resident and activated murine peritoneal macrophages. MUMP-1, MUMP-2, and MUMP-3 killed Salmonella typhimurium, Escherichia coli, Staphylococcus aureus, Listeria monocytogenes, Mycobacterium fortuitum, and Cryptococcus neoformans in vitro. MUMP-1 resembled an H1 histone but was unusual because its N-terminal residue (serine) was not N acetylated. Although MUMP-2 was N terminally blocked, its high lysine/arginine ratio and its reactivity with an antibody to H1 histones suggested that it also belonged to the H1 histone family. MUMP-3 was identical to histone H2B in 30 of 30 amino-terminal residues. Although the antimicrobial properties of histones have been recognized for decades, this is the first evidence that such proteins may endow the lysosomal apparatus of macrophages with nonoxidative antimicrobial potential. Other MUMPs, including some with a more restricted antimicrobial spectrum and one that appeared to be induced in RAW264.7 cells after gamma interferon stimulation, were noted but remain to be characterized.
Department of Infectious Diseases, University Hospital Leiden, The Netherlands.
P S
PS
Hiemstra
P B
PB
Eisenhauer
S S
SS
Harwig
M T
MT
van den Barselaar
R
R
van Furth
R I
RI
Lehrer
D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000032:analysis / Q000737:chemistry / Q000302:isolation & purification*; D002460:Cell Line; D003594:Cytoplasmic Granules / Q000737:chemistry; D005260:Female; D006657:Histones / Q000032:analysis; D007371:Interferon-gamma / Q000494:pharmacology; D008264:Macrophages / Q000737:chemistry*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D009113:Muramidase / Q000032:analysis; D011506:Proteins / Q000302:isolation & purification*
D000890:Anti-Infective Agents; D006657:Histones; D011506:Proteins; D007371:Interferon-gamma; D009113:Muramidase