Deficient induction of leukotriene synthesis in human neutrophils by
lipoxygenase-deficient platelets
K Kanaji, M Okuma and H Uchino
The effect of human platelets with deficient lipoxygenase activities on
leukotriene B4 (LTB4) synthesis by neutrophils was studied. When
arachidonic acid (AA) metabolites obtained from the incubation of washed
normal neutrophils and platelets with N- formylmethionylleucylphenylalanine
(FMLP), cytochalasin B, and AA were analyzed by reversed-phase
high-performance liquid chromatography, the synthesis of 5-lipoxygenase
products, including LTB4, was remarkably stimulated by platelets, with
their maximal effect at a ratio of platelets to neutrophils of 15:1.
However, the use of lipoxygenase- deficient platelets obtained from four
patients with myeloproliferative disorders instead of normal platelets
showed the deficient production of 5-lipoxygenase-derived products, whereas
platelets with normal lipoxygenase activities obtained from MPD patients
stimulated the 5- lipoxygenase pathway similarly to the way in which normal
platelets did. The addition of 12-hydroperoxyeicosatetraenoic acid
(12-HPETE), a labile AA metabolite via the platelet lipoxygenase pathway,
could activate the 5-lipoxygenase pathway in neutrophils incubated with
FMLP, cytochalasin B and AA, but its stable end product, 12-
hydroxyeicosatetraenoic acid, could not. Thus, it is suggested that
lipoxygenase-deficient platelets did not sufficiently stimulate LTB4
synthesis during platelet-neutrophil interactions because of defective
formation of 12-HPETE. This altered interaction between platelets and
neutrophils through the lipoxygenase pathway might result in deficient
responses at sites of thrombosis or inflammation in patients with deficient
platelet lipoxygenase activities.
Volume 67,
Issue 4,
pp. 903-908,
04/01/1986
Copyright © 1986 by The American Society of Hematology
