5-Lipoxygenase pathway-derived products of
arachidonic acid released by human eosinophils activated in vitro have been measured by using radioimmunoassays specific for
leukotriene B4 (
LTB4) and for sulfidopeptide
leukotrienes including
leukotriene C4 (
LTC4). Eosinophil-enriched leukocytes (mean, 85% eosinophils) from five hypereosinophilic donors activated with 5.0 microM
ionophore A23187 for 15 min at 37 degrees C in the presence of 50 mM
L-serine released 69 +/- 28 and 1.5 +/- 0.8 (mean +/- SEM) ng of
LTC4 and
LTB4, respectively, per 10(6) cells; ratios of
LTC4 to
LTB4 ranged from 16 to 149. Eosinophils stimulated with
ionophore (2.5 microM) or
phorbol myristate acetate (1 microgram per ml) metabolized exogenously added
LTC4 to products that coeluted on reverse-phase high-performance liquid chromatography with synthetic S-diastereoisomeric
LTC4 sulfoxides and 6-trans-LTB4 diastereoisomers, and this metabolic inactivation was inhibited by
L-serine or
catalase.
Ionophore-activated eosinophils purified from three normal donors also preferentially generated
LTC4 (38 +/- 3 ng per 10(6) cells) relative to
LTB4 (6.0 +/- 3.1 ng per 10(6) cells), whereas neutrophils from the same donors released
LTB4 (48 +/- 21 ng per 10(6) cells) in a greater than 7-fold excess to
LTC4. The predominant production by human eosinophils of
LTC4 with its potent smooth muscle spasmogenic and vasoactive properties may contribute to the pathobiology of allergic and other diseases associated with
eosinophilia.