PEPTIDE NAF/NAP-1 INDUCES HISTAMINE AND LEUKOTRIENE RELEASE BY INTERLEUKIN 3-PRIMED BASOPHILS

Basophilsareaninfrequent typeofleukocytethatbearhighaffinity IgEreceptors,containimportantamountsofhistaminein theirgranules,andarecapableofgener-atinghighlevelsofsulfidoleukotrienes. TheyareactivatedafterIgEreceptor cross-linking, andtheirproducts lead to thewell-knownsigns ofimmediate-typehyper-sensitivity (1). Basophils are also activated by IgE-independent mechanisms, andmaythuscontributeto nonallergicinflammatoryresponses. Sofartwowell-definedchemotactic peptides, the anaphylatoxin C5aandthe bacterial product analogueFMLP,have been shownto inducebasophil degranulation (1, 2). In addition, sev-eralcell-derived factorshavebeenrepeatedlyimplicated in basophilactivation. How-ever, upto nownodefinedandpurecytokine wasfoundtohaveapotentandconsis-tent histamine-releasing activityforbasophilsincubatedinphysiologicalbuffers(3,4).NAF/NAP-1 is anovel neutrophil-activatingpeptide that wasoriginally isolatedfromtheculturefluidsofstimulated humanmonocytes(5-7), andwassubsequentlyshownto beproducedby avarietyofdifferentcells (reviewedin reference8). LikeC5aandFMLP,NAF/NAP-1 activates humanneutrophils, inducingchemotaxis,shapechange, granulerelease, andthe respiratoryburst(8). Inthis paperweshowthat NAF/NAP-1 induces therelease ofhistamine andleukotriene C4 (LTC4) fromhumanbasophilsthat have been exposed to IL-3. Ourresults indicatethat in thepresenceofIL-3, NAF/NAP-1 fulfills the role ofa"histamine-releasing factor"andmaythus mediateIgE-independent hypersensitivity reactions.