乳児期より難治性口腔内カンジダ症を反復した姉弟の単球は走化能,カンジダ貪食殺菌能,IL-1産生能に異常を示したが,好中球機能やTおよびBリンパ球機能は正常であった。これらのことから真菌に対する感染防御の上で単球は重要な役割を果たしていると思われる。血球貪食症候群患児の血中サイトカイン濃度を測定し,臨床症状,検査所見の推移と比較した。2例とも増悪期においてIFN-γは著明な高値を示したが,TNF-αは全経過を通して正常範囲内であり,IL-1β, GM-CSFも正常もしくは軽度の上昇にとどまった。これらの結果はHPSでみられる組織球の活性化にIFN-γが最も重要な役割を演じていることを示している。JCMLのGM造血前駆細胞は種々のサイトカインの単独あるいは組み合わせに反応して正常骨髄よりも多数の,より大きなコロニーを形成し,増殖した細胞の大部分はマクロファージであった。また,JCMLのGM前駆細胞は正常対照と比較してtyrosine kinase inhibitorに抵抗性を示したことから,本症ではサイトカインによるparacrine増殖だけでなく造血幹細胞自体にも異常があることが示唆された。
単球,マクロファージは貪食殺菌能に加えて,抗原提示能,サイトカイン分泌能を有し,リンパ球との間で巧妙な免疫機構を構築している。マクロファージを活性化するサイトカインにはinterleukin-1 (IL-1), tumor necrosis factor (TNF), interferon-γ (IFN-γ), granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF)などがある。
単球,マクロファージの機能異常をきたす疾患の臨床像,病態についてはいまだ不明な点が多い。本稿では,単球,マクロファージの機能異常を機能低下と機能亢進に分け,サイトカインとの関連を中心にわれわれの成績を述べ,これらの病態について検討した。

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We reviewed roles of human alveolar macrophages (AM) in the pathogenesis of some diseases of the lung, based mainly on our own experimental results. Two main subjects were as follows;
1) Effects of smoking and pretreatment with lipopolysaccharide on superoxide anion and leukotriene B₄ secretion from AM in association with the pathogenesis of emphysema and adult respiratory distress syndrome (ARDS).
2) Effects of certain macrophage-active cytokines on Mycobacterium avium complex (MAC) growth in AM in combination with myeloperoxidase in association with the pathogenesis of primary MAC infection in the lung.
In conclusion, hyperactivated state of AM might cause some forms of inflammatory lung disease, such as emphysema, pulmonary fibrosis, and ARDS, while some defects of their function might cause some forms of chronic pulmonary infection, such as primary MAC disease. The demonstration of the real role of AM in the disease process are worth pursuing in the future study.

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We report the results of in vitro experiments and in vivo studies to explore the possibility whether macrophage function might influence on the prognosis of human leukemia. At first, we noticed a transient but remarkable monocytosis during recovery after intensive chemotherapy in peripheral blood of patients with acute leukemia. Such remarkable monocytosis was observed only when they achieved a complete hematological remission. This may reflect the recovery of normal hematopoiesis, in addition, monocytes might contribute to the reduction of residual leukemic cells. To explore such possibility, we took advantage of monocyte-derived macrophages (Mφ). Mφ, pretreated with IFN-γ or LPS, lysed human leukemic cells, HL-60 and K562. When Mφ were pretreated with IFN-γ and LPS simultaneously, they lysed much more leukemic cells. Furthermore, activated Mφ could induce lysis of leukemic cells separated from Mφ by a microporous membrane. As to the mechanism of leukemic cell lysis by activated Mφ, TNF was found to be at least an important effector molecule. It was also suggested that TNF and other labile factor(s) might be involved in the leukemic cell lysis. Next, we measured the concentration of various cytokines in the blood of leukemia patients before chemotherapy, at nadir, and on recovery phase. Among them, the concentration of IL-6 was high on recovery phase. G-CSF was high at early recovery phase in the blood of some patients. In the patients with high grade fever the concentration of G-CSF, M-CSF, and IFN-γ was high. Elevated concentration of IL-6 may contribute for early recovery of normal blood cells.
Monocyte-derived Mφ of patients with leukemia, obtained during monocytosis, lysed HL-60 to a similar extent as control Mφ. The finding that activated human Mφ could lyse human leukemic cells suggests a role of Mφ in the eradication of leukemic cells in vivo and supports the possibility of clinical application of activated Mφ.

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We examined the role of monocyte-macrophages (MO/MAC) in hemostatic disorder. Plasma cytokine levels, such as interleukin-1β (IL-1β) and tumor necrosis factor (TNF) were higher in patients with hemophagocytic syndrome (HPS) associated severe hemostatic disorder and organ failure. These cytokine levels were also increased in patients with disseminated intravascular coagulation (DIC), suggesting that the activation of MO/MAC is involved in the pathogenesis of hemostatic disorder.
Tissue factor (TF) activity and plasminogen activator (PA) activity in leukemic cells were significantly higher in DIC patients than in non DIC patients. PA inhibitor-II antigen in leukemic cells was highest in acute monocytic or myelomonocytic leukemia (AMoL/AMMoL). Those patients showed hypercoagulant-hypofibrinolytic state and organ failure, suggesting that PAT-II played an important role in the hemostatic abnormalities.
In the study of cultured MO/MAC, IL-1β elevated TF activity and PAI-II antigen in MO/MAC lysate, their culture medium significantly elevated TF and PAI-I production of human umbilical vein endothelial cells (HUVEC). Lipoproteins also had the capacity to elevate TF production of MO/MAC.
These finding suggested that MO/MAC play a very important role in thrombogenesis and organ failure by secretion of cytokines and/or expression of TF and PAI-II.

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In this study the correlation between Epstein-Barr virus (EBV) and non-Hodgkin's lymphoma (NHL) arising in the patients from Jilin province, China and Akita prefecture, Japan, were comparatively analysed. 108 cases in Jilin and 101 cases in Akita were examined for EBV latent membrane protein antigen expressed by immunohistochemical procedures using monoclonal antibody, LMP-1. Activation-and transformation-associated EBV LMP-1 was detected in Jilin in twelve (11.1%) cases of 108 NHL, comprising ten (10.3%) diffuse and two (18.2%) follicular type, and ten (10.9%) B-cell and two (12.5%) T-cell lymphomas in Jilin. In Akita, fifteen (14.9%) cases of 101 NHL, consist of fifteen (15.0%) diffuse and none follicular type, and seven (9.3%) B-cell and eight (30.8%) T-cell lymphomas were expressed LMP-1 positive. No particular difference in positive rate was noted among each subtypes of NHL in both areas.
There were some variaties in the size of LMP-1 positive cells, but mostly they were large, transformed immunoblasts in every subtype.
In Jilin, twelve with LMP-1 positive cases were consisted six (10.2%) of nodal and six (12.2%) of extranodal NHL. The nodal lymphomas showing LMP-1 positive more often in retroperitoneal (22.2%) and mesenteric (20.0%) lymph nodes, and the extranodal lymphomas were often seen in small intestines (25.0%). In Akita, fifteen with that were consisted six (11.3%) of nodal and nine (18.8%) of extranodal NHL. The nodal one showing higher positive rate in cervical glands (12.5%) and the extranodal one in Waldeyer's rings (27.3%).
It would be very interesting that this study showed the surprisingly frequent expression of EBV LMP-1 in the predominant sites of NHL in both areas.

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