Levitz S M, Farrell T P
Evans Memorial Department of Clinical Research, University Hospital, Boston University Medical Center, MA 02118.
J Leukoc Biol. 1990 Feb;47(2):170-5. doi: 10.1002/jlb.47.2.170.
Previous studies have established that human neutrophils (PMN) are unable to kill resting conidia (RC) of Aspergillus fumigatus but can kill conidia that have been preincubated in culture medium until swollen but not yet germinated. Compared with swollen conidia (SC), RC stimulate a relatively weak PMN respiratory burst. In the present study, we further examined the mechanisms of resistance of RC to neutrophil killing by comparing neutrophil degranulation and phagocytosis following stimulation by RC and SC opsonized in pooled human serum. RC, compared with SC, stimulated significantly less release of both the primary granule marker beta-glucuronidase and the secondary granule marker lactoferrin. PMN also phagocytosed significantly greater numbers of SC, although the differences in phagocytosis were not great enough to account for the differences in degranulation. Suboptimal stimulation of degranulation and phagocytosis may thus contribute to the inability of neutrophils to kill RC. Moreover, reagent lactoferrin bound avidly to both RC and SC, raising the possibility that PMN-released lactoferrin may contribute to antifungal activity at the conidial surface by competing for iron or catalyzing the formation of oxygen radicals.
以往的研究表明，人类中性粒细胞（PMN）无法杀死烟曲霉的静止分生孢子（RC），但能够杀死在培养基中预孵育至肿胀但尚未萌发的分生孢子。与肿胀的分生孢子（SC）相比，RC刺激PMN产生的呼吸爆发相对较弱。在本研究中，我们通过比较在人混合血清中调理后的RC和SC刺激后的中性粒细胞脱颗粒和吞噬作用，进一步研究了RC对中性粒细胞杀伤的抗性机制。与SC相比，RC刺激后，初级颗粒标志物β-葡萄糖醛酸酶和次级颗粒标志物乳铁蛋白的释放均显著减少。PMN吞噬的SC数量也明显更多，尽管吞噬作用的差异不足以解释脱颗粒的差异。因此，脱颗粒和吞噬作用的次优刺激可能导致中性粒细胞无法杀死RC。此外，试剂乳铁蛋白与RC和SC都有强烈结合，这增加了PMN释放的乳铁蛋白可能通过竞争铁或催化氧自由基的形成而在分生孢子表面发挥抗真菌活性的可能性。
