Release of slow reacting substance of anaphylaxis from human leukocytes

Mediators of immediate hypersensitivity were released from human leukocytes by means of allergen challenge. Leukocytes from 12 consecutive donors were challenged with allergens to which these donors were clinically sensitive. In all, histamine and a second substance (SRS A(leuk)) which caused prolonged contraction of guinea pig ileum, were released. No SRS A(leuk) was obtained without allergen challenge, and none was observed from nonatopic leukocytes challenged with the same allergens. The time of release after addition of allergens and the allergen dose response curves for release of both histamine and SRS A(leuk) were quite similar. SRS A(leuk) was synthesized de novo after allergen challenge since this factor was not demonstrated in disrupted cells. SRS A(leuk) was soluble in 80% ethanol and was not destroyed by base hydrolysis. The smooth muscle contracting activity of SRS A(leuk) resembled that of slow reacting substance of anaphylaxis (SRS A) obtained from human lung and rat peritoneal cells, but was different from histamine, bradykinin, serotonin, and prostaglandin E₁ and F(2α). Preliminary studies suggest that both histamine and SRS A(leuk) are synthesized by human basophils. It is concluded that SRS A is generated by human leukocytes as well as human lung and nasal polyps, and suggest that this mediator may play an important role in the pathogenesis of human immediate hypersensitivity reactions.