Complexes of DNA with the Antimicrobial Peptide LL37 Augment NK Cell Functions by Inducing Type I Interferon Production from Circulating Monocytes and Plasmacytoid Predendritic Cells.

The cationic antimicrobial peptide, LL37, forms electrostatic complexes with DNA (LL37-DNA), which are potent activators of circulating plasmacytoid predendritic cells (ppDCs) and monocytes. However, the effects of LL37-DNA on other immune cell types, such as NK cells, are poorly characterized. In this study, we show that complexes of human genomic DNA (hgDNA) or synthetic double-stranded oligodeoxynucleotides with LL37 strongly enhance natural cytotoxicity of human peripheral blood mononuclear cells (PBMCs) upon an overnight culture, whereas hgDNA alone has no effect, and LL37 alone is moderately active. LL37-DNA complexes potentiate degranulation of, and interferon (IFN)-γ production by, NK cells upon subsequent encounter of K562 target cells. The complexes do not influence percentages of NK cells among PBMCs or the expression of cytotoxic proteins by NK cells. Using neutralizing anticytokine antibodies and immunomagnetic depletion of different subpopulations of PBMCs, we found that the effect of LL37-DNA on NK cells is indirect and mediated by type I IFNs produced by monocytes and, to a lesser extent, by ppDCs. We discuss possible roles of LL37-DNA complexes in the regulation of NK cell functions and in the treatment of cancer.

Testicular isoform of angiotensin I-converting enzyme (ACE, CD143) on the surface of human spermatozoa: revelation and quantification using monoclonal antibodies.

PROBLEM: The elucidation of the role of angiotensin-converting enzyme (ACE, CD143) in the male fertility has been hampered by the absence of highly specific antibodies to the native testicular isoform (tACE). The quantification of tACE expression on human-ejaculated spermatozoa was performed using a novel panel of monoclonal antibodies (mAbs). METHOD OF STUDY: The expression of tACE on the surface of live and fixed human spermatozoa was analyzed by flow cytometry and immunocytochemistry using new mAbs to human tACE. RESULTS: Monoclonal antibodies 1E10 and 4E3 similarly revealed tACE on the surface of live and fixed spermatozoa. The high percentage of tACE-positive spermatozoa (median 81%) was revealed in the swim-up fraction of sperm. Antibody-induced tACE shedding occurs preferentially from live sperm with defective function and/or morphology. Testicular ACE is located on the plasma membrane of the post-acrosomal region, the neck and midpiece of normal spermatozoa, but showed a variable distribution on the defective cells. CONCLUSIONS: The new mAbs recognizing the C-terminal domain of human ACE are useful tools for quantification of tACE expression on human live and fixed spermatozoa and further adequate analysis of the tACE role in reproduction.

Effect of a levonorgestrel intrauterine system on women with type 1 diabetes: a randomized trial.

OBJECTIVE: Women with diabetes need safe, effective contraception. Although intrauterine devices provide superior contraception, concerns remain that progestin absorbed systemically from the levonorgestrel-releasing device may impair carbohydrate metabolism. To examine the effect of the levonorgestrel-releasing intrauterine system on glucose metabolism in diabetic women. METHODS: We randomly assigned 62 women with uncomplicated insulin-dependent diabetes mellitus to either a levonorgestrel-releasing or a copper T 380A intrauterine device. The primary outcome to assess glucose metabolism was glycosylated hemoglobin; fasting serum-glucose levels and daily insulin dose requirements over 12 months of observation were examined as well. RESULTS: Outcome data were available for 29 women using the levonorgestrel-releasing and 30 using the copper device. At 12 months, mean glycosylated levels were similar for women of the 2 groups (6.3%, standard deviation [SD] +/- 1.5 compared with 6.3%, SD +/- 1.3, respectively). The same was true for mean fasting-serum glucose levels (7.4 mM, SD +/- 4.2 compared with 7.5 mM, SD +/- 4.2) and daily insulin doses (35.1 units, SD +/- 12.8 compared with 36.4 units, SD +/- 9.0). No important differences were noted at either 6 weeks or 6 months. CONCLUSION: The levonorgestrel-releasing device had no adverse effect on glucose metabolism, even at the 6-week observation when systemic levels of levonorgestrel would have been higher than at later observations. Concern about a potential adverse effect of this contraceptive on glucose control is unwarranted, and its use in women with diabetes should be liberalized. LEVEL OF EVIDENCE: I.