RAPID COMMUNICATION Vesicular Transport of Histamine in Stimulated Human Basophils

Human basophils participating in experimentally produced contact allergy display progressive secretion of electrondense secretory granule contents and retention of cytoplasmic granule containers in the absence of entire granule extrusion, a process termed piecemeal degranulation (PMD) and postulated to be effected by vesicular transport (Dvorak HF, Dvorak AM: Clin Hematol4651, 1975). Proof of this hypothesis was sought using models of human basophil-stimulated secretion, partially purified human peripheral blood basophils, and a morphometric analysis of the fraction of total cellular cytoplasmic vesicles loaded with histamine, a major proinflammatory mediator present in basophil secretory granules. The subcellular localization of histamine was accomplished using a new ultrastructural enzyme-affinitygold method based on the affinity of diamine oxidase for its substrate, histamine (Dvorak et al: J Histochem Cytochem 41:787, 1993). Two models were selected for a kinetic analysis of stimulated vesicle transport of histamine based on known biochemical and ultrastructural characteristics (MacGlashan et al: J lmmunol 136:2231, 1986; Warner et al: ./ LeukocBio/45:558,1989; Dvorak et al: Am Jfathol141:1309, 1992; Dvorak et al: Lab lnvest W234, 1991). These models were selected to include the rapid release reaction stimulated by the bacterial peptide, FMLP, and the slow release reaction stimulated by the phorbol diester tumor promoter,