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Armed human monocytes challenged with a sensitizing cancer extract release substances pharmacologically similar to leukotrienes
Author(s) -
Thomson D. M. P.,
Phelan Kerry,
Morton Douglas G.,
Bach Michael K.
Publication year - 1982
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910300308
Subject(s) - leukotriene , peripheral blood mononuclear cell , monocyte , leukotriene b4 , immunology , platelet activating factor , leukotriene c4 , u937 cell , medicine , cancer cell , pharmacology , cancer , chemistry , inflammation , in vitro , biochemistry , asthma
Human peripheral blood monocytes were highly enriched by adherence to plastic, armed with serum from cancer patients, and challenged separately and simultaneously with the sensitizing and unrelated cancer extracts. The response of the monocytes was to release a factor that inhibited leukocyte adherence (LAI) 4 to glass. The macrophage‐like cell line U937 released a similar factor when it was armed and challenged with the sensitizing cancer extract. The production of the factor was blocked by 10 −6 M ETYA and 10 −6 M NDGA but not by 10 −6 M indomethacin. Moreover, a competitive inhibitor of leukotriene function, 10 −6 M FPL55712, blocked the LAI reaction mediated by the factor. Arylsulfatase destroyed its activity while depletion of the monocytes' cellular glutathione pool with CyH or Et 2 Mal stopped production of the mediator. Pure leukotrienes (C and D) in a dose‐response fashion prevented the adherence of leukocytes to glass; the nonadherence of mononuclear cells was equal to that of polymorphonuclear cells. PGE 2 , if added to the leukocytes immediately before challenge with LTC or LTD, increased 1,000‐fold the leukocytes' sensitivity to the leukotrienes. Paradoxically, if leukocytes were washed and exposed to PGE 2 15 min after being challenged with leukotrienes, their normal glass‐adherence property and the ability to respond again to LTD were restored. FPL 55712 blocked the effect of LTC and LTD from inhibiting the adherence of leukocytes to glass. The present study shows that human monocytes armed with cytophik antitumor antibody, when challenged with the sensitizing cancer extract, release leukotriene(s) as shown by pharmacologic evidence, implying that monocytes may play an important inflammatory role in human cancer.