Bandholtz L, Ekman G Jacobsson, Vilhelmsson M, Buentke E, Agerberth B, Scheynius A, Gudmundsson G H
Department of Medicine, Clinical Allergy Research Unit, Karolinska Institutet and University Hospital, Stockholm, Sweden.
Scand J Immunol. 2006 Jun;63(6):410-9. doi: 10.1111/j.1365-3083.2006.001752.x.
The human cathelicidin LL-37 has been shown to be involved in the barrier function of the innate immunity, being released from specific cells upon challenge and exerting immunomodulatory effects. We here demonstrate that LL-37 affects immature dendritic cells, derived from human peripheral blood monocytes (MDDC). LL-37 is internalized by MDDC with subsequent localization primarily in the cytoplasmic compartment. However, LL-37 could also be detected in the nuclei of MDDC, suggesting that LL-37 may be transported into the nucleus. The uptake of LL-37 is dose, time and energy dependent, indicating that the observed internalization process involves an endocytic pathway. Incubation of immature MDDC with LL-37 caused phenotypic changes, characterized by an increased expression of the antigen-presenting molecule HLA-DR, and the costimulatory molecule CD86. Taken together, these findings suggest that LL-37 released upon triggering of the innate immunity, may affect cellular adaptive immunity through an interaction with immature dendritic cells.
人源杀菌肽LL-37已被证明参与固有免疫的屏障功能,在受到刺激时从特定细胞释放并发挥免疫调节作用。我们在此证明LL-37会影响源自人外周血单核细胞的未成熟树突状细胞(MDDC)。LL-37被MDDC内化,随后主要定位于细胞质区室。然而,在MDDC的细胞核中也能检测到LL-37,这表明LL-37可能被转运到细胞核中。LL-37的摄取具有剂量、时间和能量依赖性,表明观察到的内化过程涉及内吞途径。用LL-37孵育未成熟MDDC会导致表型变化,其特征是抗原呈递分子HLA-DR和共刺激分子CD86的表达增加。综上所述,这些发现表明,在固有免疫触发时释放的LL-37可能通过与未成熟树突状细胞相互作用来影响细胞适应性免疫。