Elevated secretion of reactive nitrogen and oxygen intermediates by inflammatory leukocytes in hyperacute experimental autoimmune encephalomyelitis: enhancement by the soluble products of encephalitogenic T cells.
Perivascular lesions within the central nervous system (CNS) of rats with hyperacute experimental autoimmune encephalomyelitis (HEAE) contained large numbers of peripheral blood mononuclear cells (PBMC) and polymorphonuclear leukocytes (PMN), cells enzymatically capable of producing reactive nitrogen and oxygen intermediates (RNI and ROI), which, in excess, are mediators of tissue damage. PBMC and PMN isolated from the CNS and periphery of HEAE-affected rats secreted significantly (p less than 0.01-0.0001) elevated levels of ROI and RNI compared with that of similar cell populations from pertussis- and saline-treated control animals. Coincubation of systemically derived PBMC and PMN with antigen-stimulated myelin basic protein-specific T cell lines led to further increases in ROI and RNI output of between 15.3 and 83.1%, an effect that could be largely attributed to heat-labile, soluble products released by these T cell lines. Our studies suggest a putative neuropathological role for ROI and RNI in HEAE, which may be mediated via cytokines emanating from autoreactive T lymphocytes.
MacMicking
J D
JD
Division of Cell Biology, John Curtin School of Medical Research, Canberra, Australia.
Willenborg
D O
DO
Weidemann
M J
MJ
Rockett
K A
KA
Cowden
W B
WB
D000818:Animals; D002460:Cell Line; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism*; D007371:Interferon-gamma / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism*; D009584:Nitrogen / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D013481:Superoxides / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D007371:Interferon-gamma; D009584:Nitrogen; D010100:Oxygen