NOTES Fungicidal Components of Mammalian Granulocytes Active against Cryptococcus neojormons

Citric acid extracts of granule-rich fractions, prepared from rabbit and guinea pig heterophils or human neutrophils, killed Cryptococcus neoiormans in vitro. These extracts were fractionated by micropreparative electrophoresis on polyacryla-mide gels. In preparations of rabbit and guinea pig heterophils, cryptococcidal activity was associated predominately with lysosomal cationic protein complex. Hu-man neutrophils lacked strictly comparable cationic proteins but contained other components that killed C. neojormans. These components appeared to be identical to previously described proteins of the human neutrophil active against Candida parapsilosis. CTyptococcuS neoiormans, a fungus of cosmo-politan distribution, can coexist with humans in a state of commensalism, unassociated with overt disease [1], or it may cause localized or dissemi-nated infections. Despite the well-recognized op-portunistic proclivities of C. neoiormans, it also produces disease in patients without evident pre-disposing causes. Multiple host defense mechanisms may con-tribute to resistance against this organism. These mechanisms include specific antibodies [2], cell-ular histones and other basic proteins [3], com-plement components [4,5], activated macrophages [6], lymphocytes [7], granulocytes [8, 9], and extracellular factors elaborated by mononuclear blood cells [10] or macrophages [11]. That human blood granulocytes and mono-cytes can ingest and kill C. neoiormans has re-cently been emphasized [9, 12]. Previous investi-gations in our laboratory est~blished the exis-tence of two general fungicidal mechanisms en-abling human neutrophils to kill Candida spe-cies. One of these mechanisms, which is oxygen-de-Received for publication December 22, 1975, and in reo vised form January 17, 1977