Morito Sumiya

Medullasin enhances human natural killer cell activity.

Medullasin, a new serine protease found in bone marrow cells, increased markedly human natural killer cell activity. Whereas the natural killer cell activity measured immediately after the treatment with medullasin remained almost on the same level as the control, an incubation at 37 degrees C for several hours increased markedly the natural killer cell activity of the lymphocytes treated with medullasin. Enhancement of the natural cytotoxicity was caused by the treatment with physiologic concentrations of the protease (5-20 micrograms/ml). Inhibitors of medullasin such as phenylmethylsulfonyl fluoride and elastatinal prevented the activation of natural cytotoxicity. Depletion of lymphocytes bearing Fc receptors for IgG abolished the enhancement of natural killer cell activity by medullasin. Interferon activity was not detected in the supernatant of lymphocyte cultures stimulated with medullasin. The medullasin enhanced further the natural killer cell activity of lymphocytes stimulated with interferon. Medullasin activity was detected neither in unstimulated nor stimulated (by concanavalin A or phytohemagglutinin) human lymphocytes. The protease was released easily from human mature granulocytes into culture medium. It is considered from these results that the level of human natural killer cell activity is regulated by medullasin released by mature granulocytes.

Adult onset mucocutaneous lymph node syndrome with coronary aneurysm

1. Ciraulo DA: Mitral value fluttering. An ecbocardiographic feature of left atria1 myxoma. Chest 7’695, 1979. 2. Bourdillon PDV, Monro JL

Stimulation of Human Lymphocyte Subpopulations by Protein A from Staphylococcus aureus

Johnson AM: Left atria1 myxoma with aortic regurgitation. Br Heart J 40575, 1978. 3. Clark RD: Case studies m echocardiograpby. A diagnostic workbook. Philadelphia, 1977, W. B. Saunders Co, pp 76. 4. Rose MR, Fox AC, Glassman E, Reed GE: Left atria1 myxoma and aortic regnrgitation Case report. J Thorac Cardiovasc Surg 66:797, 1974.

Natural killer cell activity in untreated systemic lupus erythematosus

Protein A from Staphylococcus aureus is known to stimulate human lymphocytes. Using 3H-thymidine incorporation, virus plaque assay and induction of cytotoxic T lymphocytes (CTL), this study showed that soluble or insoluble protein A stimulated different lymphocyte subpopulations. Soluble protein A is highly mitogenic to T lymphocytes. In both 3H-thymidine incorporation and virus plaque assay, its maximum stimulation was as high as the stimulation by the nonspecific mitogens phytohemagglutinin and concanavalin A, and a higher CTL response than that induced by phytohemagglutinin or concanavalin A was induced. Mitogenic activity to B lymphocytes was negligible. S. aureus (Cowan I strain) is itself considered to be an insoluble form of protein A and is 3--4 times more mitogenic to B lymphocytes than pokeweed mitogen without any increase in virus plaque-forming cells. No mitogenicity was noted to T lymphocytes. Sepharose CL-4B-protein A, also known as insoluble protein A, stimulated both T and B lymphocytes effectively, but its mitogenicity to T lymphocytes was considered to be due to the soluble protein A released from the Sepharose CL-4B beads.

Cytotoxicity of Cultured Mouse Spleen Cells against Natural Killer-Sensitive Target Cells

With strictly selected controls natural killer cell activity was evaluated in 10 untreated patients with systemic lupus erythematosus. Natural killer levels of the patients were significantly lower than those of the age- and sex-matched normal controls. Natural killer levels, however, did not correlate with disease activity.

Induction of Cytotoxic Lymphocytes by Protein A Derived from Staphylococcus aureus

Killer cells with natural killer (NK) cell-like target selectivity were generated when C3H or C57BL/6 mouse spleen cells were cultured in vitro. Compared with NK cells, the in vitro-generated killer cells with NK-like reactivity were slightly adherent to nylon wool fibers, a little more sensitive to anti-Thyl.2 antibody plus complement and almost entirely resistant to cytotoxic treatment with anti-asialo GM1 antiserum which is selectively cytotoxic to NK cells. The culture of NK-depleted spleen cells yielded a lower degree of NK-like cytotoxicity, thus it seems likely that NK cells changed to NK-like killer cells in vitro. Competitive inhibition studies suggested that the in vitro-generated NK-like cells were different from alloantigen-reactive killer T cells. The above results, therefore, might suggest that in vitro-induced NK-like cells do not belong to any known subset of killer cells.

Letter: Chronic lymphocytic leukaemia of T-cell origin?

Protein A (pA) from Staphylococcus aureus is known to be a good mitogen for human T lymphocytes. In this study, the cytotoxic activity of pA-activated lymphocytes was assessed using human lymphoblastoid cell lines (LCL) as target cells. pA induced higher cytotoxic activity against LCL on the 3rd day of incubation than phytohemagglutinin or concanavalin A. However, it was necessary for pA to be present in the assay for these pA-activated lymphocytes to manifest their cytotoxicity. Cytotoxic activity was not detected in a control culture in which pA was added at the assay, nor was it detected in the supernate of pA-activated culture. These data suggest that the cytotoxicity of these lymphocytes was pA-activated, pA-dependent cell-mediated cytotoxicity, pA-activated, pA-dependent cytotoxicity was mediated by T lymphocytes and was induced from Fc-receptor-negative [Fc(-)] T lymphocytes. The effector cells were mainly Fc(-) T lymphocytes. The relationship between pA-activated, pA-dependent cytotoxicity, lectin-dependent cellular cytotoxicity and alloantigen-induced cytotoxic T lymphocytes is also discussed.