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The characteristics of histamine release induced by human leukocyte lysates were determined. Intact human leukocytes released histamine during incubation with leukocyte lysates. Maximal release occurred under physiological conditions of temperature and pH, and both Ca(2+) and Mg(2+) were required. The addition of ethylenediaminetetraacetic acid abruptly inhibited release. Complement was not required, and serum actually inhibited release. Histamine release was maximal at lysate concentrations of 0.25 to 1.0 mug of protein per ml, and it was reduced at either higher or lower concentrations. Leukocytes continued to exclude trypan blue and maintained chemotactic activity after histamine release. Leukocytes released histamine independently of cellular protein or enzymes. Histamine release induced by leukocyte lysates was interrupted by subsequent removal of the lysate. The data suggest that this histamine release occurs by a specific, complement-independent, noncytotoxic process which resembles, but is not identical with, antigen-induced histamine release. The system has several unique characteristics which suggest that it is a novel form of inflammatory histamine release. This system should provide a useful in vitro model for studies of cellular processes in human inflammation.

Histamine Release Induced by Human Leukocyte Lysates: Implication of a Specific, Complement-Independent, Noncytotoxic Reaction