A novel epitope of N-CAM defines precursors of human adherent NK cells

Activated, adherent natural killer (A-NK) cells represent a distinct subpopulation of interleukin (IL)-2-stimulated NK cells, which are selectively endowed with the increased expression of integrins and ability to adhere to solid surfaces, migrate into, infiltrate, and destroy cancerous tissues. The present study defines the phenotype and functions of precursors of A-NK (pre-A-NK) cells in humans. Peripheral blood pre-A-NK cells, in contrast to the rest of NK cells, express a novel epitope of CD56 neuronal cell adhesion molecule, termed ANK-1, and increased cell-surface levels of integrins. Pre-A-NK cells also express low levels of CD56 and CD161, and some express CD162 receptor, do not express CD25 or activation markers, and are effective mediators of NK cytotoxicity. Thus, pre-A-NK cells are generally similar to CD56(dim) NK cells. However, pre-A-NK cells differ from the main NK cell subpopulation by having a lower expression level of CD16 and a lower ability to mediate redirected antibody-dependent, cell-mediated cytotoxicity. More importantly, pre-A-NK cells are preferentially endowed with the ability to rapidly respond to IL-2 by integrin-mediated adherence to endothelial cells, extracellular matrix, and plastic. This early, specific response of pre-A-NK cells to IL-2 is followed by their activation, vigorous proliferation, and differentiation into phenotypically and functionally similar A-NK cells. Pre-A-NK cells represent only approximately 26% of peripheral blood NK cells but encompass the majority of NK cells in normal and cancerous, solid tissues. We conclude that pre-A-NK cells represent a distinct subset of resting, mature NK cells with the characteristics indicative of their ability to migrate and reside in solid tissues.     

Identification of delta- and mu-type opioid receptors on human and murine dendritic cells.

The purpose of this study was to evaluate mu- and delta-opioid receptors (OR) on human and murine dendritic cells (DC). Expression of mu- and delta-OR mRNA on DC was demonstrated by RT-PCR. The immunocytochemical and Western blot analyses revealed the expression of OR protein in DC. Radioreceptor assay demonstrated the specific saturated temperature-dependent binding of [3H]-labeled opioid ligand on DC and B(max)=2.8+/-0.3 fmol/10(6) cells and K(D)=4.8+/-1.0 nM were calculated by a Scatchard analysis. Finally, OR ligands DADLE and DAGO dose-dependently modulated the capacity of DC to induce T cell proliferation in an MLR assay. Importantly, expression of functional OR on DC was significantly increased upon TNF-alpha-induced DC maturation. Thus, these data suggest a new mechanism of opioid-dependent neuroendocrine immunomodulation.     

A rational use of immune enhancing diets: when should we use dietary arginine supplementation?

Controversies in any arena of human activity often result in the polarization of the individuals involved into 2 opposing camps. Controversy about the use of immune-enhancing diets (IEDs) is no exception. On one hand, some groups are proposing indiscriminate use of IEDs, whereas others have created guidelines advocating that their use should be banned for the critically ill. At stake is an emerging paradigm: that dietary manipulation of the immune system is possible and may become an important adjunct to other therapies, thus helping prevent or treat multiple diseases for millions worldwide. Under these circumstances, extremist claims of miraculous benefits or inappropriate assertions of evil can only delay the emergence of a nascent science. This paper is therefore a plea for moderation from both camps, lest we cause irreparable damage to our clinical practices and potential injury to individual patients. IEDs all contain arginine. However, they also contain other substances such as omega-3 fatty acids, and nucleotides. The use of all these nutrients together into commercial IEDs without adequate evaluation of their individual effects has prevented the development of mechanistic hypotheses of action. Despite this, IEDs have been tested extensively, allowing the development of guidelines for their use. IEDs should be used for surgical patients, especially those undergoing elective surgery. IEDs show no benefit and indeed can potentially harm patients with sepsis, especially in the nonsurgical group, and should not be used outside of research protocols. Advances in basic research have helped us understand mechanisms of how arginine contained in IEDs may help surgical patients but may be deleterious in patients with sepsis. A review of the basic mechanisms of action of arginine on the immune system is enclosed in this paper and should serve as a basis for the development of scientific principles that guide clinical use of IEDs.     

Development and Validation of a Quantitative Determination Method for Meropenem in Blood Plasma for Therapeutic Drug Monitoring

Pharmaceutical Chemistry Journal - The development of an HPLC method for quantitative determination of meropenem in human blood plasma for therapeutic drug monitoring in clinics is reported....     

Lung cancer-derived bombesin-like peptides down-regulate the generation and function of human dendritic cells

Development of tumors is regulated by tumor-derived neuroendocrine factors, including bombesin-like peptides (BLP). We have evaluated neuroendocrine regulation of dendritic cell (DC) maturation and function by both tumor-derived and purified bombesin (BOM), neuromedin B (NMB), gastrin-releasing peptide (GRP), and a BOM antagonist D-Phe-bombesin (DPB). BOM, NMB and GRP dose-dependently inhibited maturation of DC assessed as down-regulation of CD40, CD80 and CD86 expression on DC. BOM and GRP also inhibited interleukin-12 (IL-12) production by DC and their ability to activate T cells. DPB partly abrogated immunosuppressive effect of tumor cells on DC. These data are a first evidence for the role of BLP in the regulation of DC maturation and function, demonstrating that BLP inhibit DC maturation and longevity in the lung cancer microenvironment. This suggests a new mechanism of tumor escape and provides new targets for the immunopharmacological correction of immune effectors in cancer.