Low blood ISG15 mRNA and progesterone levels are predictive of non-pregnant dairy cows

ISG15 is induced by conceptus-derived interferon-tau in the endometrium on days 15-45 of pregnancy. It was hypothesized that pregnancy induces blood cell ISG15 gene expression and that low blood ISG15 mRNA levels provide an indication of non-pregnant cows on day 18. Blood was collected either on day 18 (n = 78) or on days 15-21, 25, and 32 (n = 21; serial collection) from dairy cows following artificial insemination (AI). Plasma progesterone concentration was determined using RIA. ISG15 mRNA levels were determined using real-time PCR. Pregnancy was diagnosed on day 32 using transrectal ultrasound. ISG15 mRNA levels increased after day 16, peaked at day 20 and then declined to day 16 levels by 32 days following AI. The average pregnancy rate was 43% based on blood cell ISG15 mRNA. The average pregnancy rate was 33% based on the transrectal ultrasound. Lower levels of ISG15 mRNA or progesterone during serial collections were 100% accurate in predicting non-pregnant cows based on day 32 transrectal ultrasound. However, detection of ISG15 mRNA yielded 78% accuracy in predicting pregnant cows, while progesterone yielded 58% accuracy. Average plasma progesterone based on pregnancy status according to ultrasound was consistently higher in pregnant (> 4 ng/ml) when compared with non-pregnant cows from days 15 to 32, except on day 16. It is concluded that detection of low blood ISG15 mRNA levels during serial collection from days 17 to 25 serves as an accurate indicator of cows that are not pregnant, thus allowing re-synchronization and insemination.     

IL-15R alpha expression on CD8+ T cells is dispensable for T cell memory

The generation and maintenance of immunological memory requires the activation, expansion, and persistent proliferation of antigen-specific T cells. Recent work suggests that IL-15 may be important for this process. Surprisingly, we now find that expression of the high-affinity receptor for IL-15, IL-15R alpha, on T cells is dispensable for the generation or maintenance of memory CD8(+) T cells. By contrast, IL-15R alpha expression on cells other than T cells is absolutely critical for this function. These findings may be related to IL-15R alpha's ability to present IL-15 in trans to low-affinity IL-15R beta gamma(c) receptors on memory CD8(+) T cells. These unexpected results provide insights into how IL-15R alpha supports memory CD8(+) T cells.     

The IL-15/IL-15Ralpha on cell surfaces enables sustained IL-15 activity and contributes to the long survival of CD8 memory T cells

We previously described unique features of the IL-15 receptor (IL-15R)alpha. IL-15Ralpha by itself forms stable complexes with IL-15 on cell surfaces and presents IL-15 in trans to neighboring natural killer/T cells. Moreover, the membrane IL-15/IL-15Ralpha complexes (membIL-15) undergo endosomal internalization but survive lysosomal degradation, allowing the complexes to recycle back to the cell surface. Here, we show that membIL-15+ cells act as a persistent source of IL-15 for the surrounding microenvironment (intercellular reservoir effect). Additionally, membIL-15+ cells give rise to augmented retention of IL-15 in the circulation as well as in tissues. Curiously, IL-15 retention was particularly associated with lungs, rather than with lymph nodes, in normal unstimulated mice, which correlated with the preferential homing of antigen-specific CD8 T cells to lungs during their contraction phase in an IL-15Ralpha-dependent manner. Furthermore, membIL-15, unlike soluble IL-15, caused sustained IL-15 signal transduction in the target cells. Collectively, these characteristics define IL-15 as a unique cytokine with prolonged in vivo survival and sustained biological action on the target cells, which may account for the proposed persistent action of IL-15 that helps the long-term survival of functional CD8 memory T cells in vivo.     

Survival adjustment of mature dendritic cells by IL-15

The survival of CD8+/CD44(hi) memory phenotype T cells depends on an IL-15 activity on nonlymphoid cells. Here, we report that IL-15 and its receptor were induced on dendritic cells (DCs) by a combination of IFN-gamma and NF-kappaB relA inducers. IL-15 conferred in an autocrine loop resistance to apoptosis that accompanied the maturation process in DCs in vitro. As an apparent result in vivo, mice deficient in IL-15 or its receptor harbor few DCs. Injecting DCs into IL-15-/- mice was associated with the appearance of CD8+/CD44(hi) T cells that depended on IL-15 expression but also correlated with the longevity of the DCs. These findings support the hypothesis that DCs mediate the effect of IL-15 on CD8+/CD44(hi) memory phenotype T cells.     

15-Lipoxygenase products stimulate prolactin secretion from a cloned strain of rat pituitary cells

Arachidonic acid and its lipoxygenase products may contribute to the process of prolactin (PRL) release. In the present study we investigate the role of 15-hydroperoxyeicosatetraenoic acid (15-HPETE) and 15-hydroxyeicosatetraenoic acid (15-HETE) on PRL secretion from GH3 cells. The incubation of GH3 cells with the lipoxygenase product 15-HETE significantly increased PRL release in a concentration-dependent manner. Nordihydroguaiaretic acid (NDGA), which reduces the production of arachidonate metabolites via the lipoxygenase pathway, also reduced basal and TRH or arachidonic-acid-stimulated-PRL release. The inhibitory effect of NDGA on PRL release could be overcome by the addition of 15-HETE. The time course curve of PRL release from cells challenged by 15-HETE had the same profile as that of cells stimulated by TRH. The stimulating effect of 15-HPETE (ED50 = 0.7 x 10(-9) M), which is the direct precursor of 15-HETE, on PRL release was greater than TRH or 15-HETE (ED50 = 6.5 x 10(-9) M). Furthermore 15-HPETE and 15-HETE seemed to affect the release of newly synthesized PRL. These data indicate that 15-HETE and 15-HPETE could be important intracellular components in the control of PRL secretion and may account for at least a part of arachidonate-induced PRL release from GH3.     

Cyclosporin A inhibits CD69 expression induced on synovial fluid and peripheral blood lymphocytes by interleukin 15

OBJECTIVE: To study the modulation of CD69 expression on peripheral blood (PB) and synovial fluid (SF) lymphocytes by interleukin 15 (IL-15) and several other cytokines and chemokines widely detected in the rheumatoid microenvironment. The effect of cyclosporin A (CSA) or methotrexate (MTX) in the cytokine mediated regulation of CD69 was analyzed. METHODS: CD69 expression on lymphocytes was assessed by flow cytometry after incubation with different cytokines, chemokines, phorbol myristate acetate, or calcium ionophore in the presence or absence of CSA, MTX, or both. The effect of IL-15 and SF supernatants in maintaining CD69 expression on SF lymphocytes was also assessed. IL-15 levels in SF supernatants were measured by ELISA. RESULTS: IL-15 induced the greatest upregulation of CD69 expression on PB lymphocytes in a time and dose dependent manner. IL-15 was able to maintain a high CD69 expression on SF lymphocytes. SF supernatants from rheumatoid arthritis (RA), which contain significant amounts of IL-15, also reversed the CD69 downregulation of SF lymphocytes in culture. CSA, but not MTX, inhibited the CD69 upregulation mediated by IL-15 both in PB and SF lymphocytes. CONCLUSION: IL-15 appears to be responsible, at least in part, for the high CD69 expression on lymphocytes from the rheumatoid microenvironment. Consistent with the virtual absence of lymphocyte derived cytokines in RA synovium, the prevention of IL-15 mediated CD69 upregulation on lymphocytes may explain the effect of CSA in the treatment of RA.     

Opposite Effects of Ro 15-4513 on Acquisition and Maintenance of Ethanol Drinking Behavior in Male Wistar Rats

Acute treatment with Ro 15-4513, a benzodiazepine receptor inverse agonist, has been consistently shown to suppress ethanol self administration behavior by rats. The aim of the present study was to examine the effect of Ro 15-4513 on the acquisition and maintenance of ethanol drinking behavior in male Wistar rats. In rats maintained on a limited access procedure with a choice of 12% w/v ethanol solution and water, acute treatment with Ro 15-4513 (0.1 to 3.0 mg/kg) suppressed ethanol intake in a selective and dose-related manner ( p < 0.01). However, by the fourth day of chronic Ro 15-4513 treatment, ethanol intake had returned to baseline levels. In contrast, chronic administration of Ro 15-4513 during the acquisition phase increased ethanol drinking behavior, compared with vehicle ( p < 0.05). To assess whether the effects of Ro 15-4513 on ethanol intake were due to an alteration in ethanol kinetics or on behavior, blood ethanol levels and rat social interaction behavior were also assessed. Neither acute nor chronic Ro 15-4513 treatment significantly altered ethanol kinetics after oral administration of ethanol (1.0 g/kg), but did suppress locomotor activity and time spent engaged in active social interaction at the 1.0 and 3.0 mg/kg doses. These results show that Ro 15-4513 has opposite effects on ethanol consumption during the acquisition and maintenance phases of ethanol drinking behavior, suggesting that different mechanisms regulate Ro 15-4513's effects on acquisition and maintenance of ethanol intake. Ro 15-4513's reported anxiogenic or memory enhancing properties may be responsible for its effects on acquisition.     

The relevance of HPA-15 antigen expression for anti-HPA-15 antibody detection

Introduction: The HPA‐15 antigen system is characterized by a low antigen expression on platelets. The antibodies against this antigen are implied in fetal/neonatal alloimmune thrombocytopenia (F/NAIT), post‐transfusion purpura, and refractoriness to platelet transfusions. Detection of these antibodies appears to be related to the level of HPA‐15 expression on the platelets used in the monoclonal antibody–specific immobilization of platelet antigen (MAIPA) assay. Methods: We performed genotyping of 300 healthy blood donors for HPA‐15 by TaqMan real‐time PCR technology, and the HPA‐15 antigen expression was investigated in 13 HPA‐15aa and 19 HPA‐15bb individuals. We also investigated the relevance of HPA‐15 antigen expression on donor platelets used in MAIPA for antibody detection in 223 multitransfused hematological patients and 271 women with suspected F/NAIT. Results: In Polish donors, the HPA‐15a allele frequencies were lower than the HPA‐15b (0.480 vs. 0.515). We identified three HPA‐15 expression groups: high (36.7 ± 8.36 MFI – eight cases), medium (19.5 ± 6.2 MFI – 21 cases), and low (6.5 ± 5.9 MFI – three cases). The HPA‐15 expression was stable over time. The HPA‐15aa and HPA‐15bb platelets with high antigen expression were used for anti‐HPA‐15 antibody detection; anti‐HPA‐15 antibodies were detected in 4/223 (1.8%) patients receiving multiple transfusions but in none of the 271 women with suspected F/NAIT. Further examination of the four sera by MAIPA with various platelets revealed the optical density in the assay to be closely related to the level of HPA‐15 antigen expression. Conclusion: Anti‐HPA‐15 antibody detection should be based on carefully selected platelets with high HPA‐15 expression level.     

Ro15-4513 Attenuates the Consumption of Ethanol in Deprived Rats

This research investigated the effects of Ro15-4513 (Ro15), a partial inverse benzodiazepine agonist, on the drinking behavior of 23-1/2 hr fluid deprived rats. Water-deprived rats were maintained on a two-bottle regimen of a saccharin-ETOH solution along with tap water available for 30 min/day for several days. Following this acclimation period, animals were pretreated with either Ro15 (1.0, 2.5, and 5.0 mg/kg) or Tween-80 vehicle injections. Pretreatment with Ro15 at all doses tested resulted in a significant reduction of the saccharin-ETOH solution; however, Ro15 did not alter the rats' consumption of water. The effects of Ro15 on general fluid consumption was investigated in Experiment 2. Following acclimation to a two-bottle regimen of a saccharin-solution and tap water 30 min/day, naive animals were pretreated with Tween-80 vehicle or Ro15 injections. Ro15 failed to alter saccharin or water consumption. The results of this study support previous reports suggesting that Ro15 attenuates the oral consumption of ETOH; however, this effect does not appear to be due to a general suppression of fluid intake.     

Development of an IL-15-autocrine CD8 T-cell leukemia in IL-15-transgenic mice requires the cis expression of IL-15Rα

IL-15 has growth-promoting effects on select lymphoid subsets, including natural killer (NK) cells, NK T cells, intraepithelial lymphocytes (IELs), CD8 T cells, and γδ-T cells. Constitutive expression of murine IL-15 in IL-15-transgenic mice was reported to cause T-NK leukemia. We investigated whether IL-15 expression is sufficient for leukemic transformation using a human IL-15-transgenic (IL-15Tg) mouse model. We noted that 100% of the mice observed over a 2-year period (n > 150) developed fatal expansions of CD8 T cells with NK markers, and determined that these cells expressed IL-15 receptor alpha (IL-15Rα). The expression of IL-15Rα on CD8 T cells appears to be required for uncontrolled aggressive lymphoproliferation, because none of the IL-15Rα(-/-)-IL-15Tg mice that we followed for more than 2 years developed the fatal disease despite controlled expansion of CD8 T cells. In addition, in contrast to IL-15Tg mice, in which leukemia-like CD8 T cells expressed IL-15Rα persistently, acutely activated normal CD8 T cells only transiently expressed IL-15Rα. Inhibition of DNA methylation enabled sustained IL-15Rα expression induced by activation. We present a scenario for IL-15Tg mice in which CD8 T cells that acquire constitutive persistent IL-15Rα expression are at a selective advantage and become founder cells, outgrow other lymphocytes, and lead to the establishment of a leukemia-like condition.     

Insulin-activated tyrosine phosphorylation of a 15-kilodalton protein in intact 3T3-L1 adipocytes.

Insulin stimulates phosphorylation of a tyrosine residue(s) on a 15-kDa protein (p15), and the cytosolic phosphorylated protein (pp15) accumulates only when 3T3-L1 adipocytes are treated with phenylarsine oxide. It has been shown previously that phenylarsine oxide, an agent that complexes vicinal dithiols, interrupts signal transmission from the insulin receptor to the glucose transport system. Several lines of evidence presented here indicate the involvement of pp15 in insulin receptor-initiated signal transduction to the glucose transport system. The reciprocal effects of phenylarsine oxide on the insulin-activated accumulation of pp15 and on insulin-stimulated hexose uptake are reversed by the vicinal dithiol 2,3-dimercaptopropanol but not by the monothiol 2-mercaptoethanol. Thus, a cellular dithiol appears to function in the signal transmission pathway downstream from pp15. Like the insulin-activated autophosphorylation of the receptor's beta subunit (on tyrosine), activation of phosphorylation of p15 is specific, with insulin-like growth factors 1 and 2, epidermal growth factor, and platelet-derived growth factor being inactive. Moreover, both processes exhibit identical insulin concentration dependence. The temporal kinetic relationship of insulin-activated receptor beta-subunit phosphorylation, followed by the phosphorylation of p15 and then increased hexose uptake rate, is consistent with an intermediary signaling role for pp15 in insulin-stimulated glucose uptake.     

Comparison of synthesis of 15 alpha-hydroxylated steroids in males of four North American lamprey species

Recent studies have provided evidence that 15 alpha-hydroxytestosterone (15 alpha-T) and 15 alpha-hydroxyprogesterone (15 alpha-P) are produced in vitro and in vivo in adult male sea lampreys (Petromyzon marinus), and that circulatory levels increase in response to injections with gonadotropin-releasing hormone (GnRH). We examined four species from the Petromyzontidae family including silver lampreys (Ichthyomyzon unicuspis), chestnut lampreys (I. castaneus), American brook lampreys (Lethenteron appendix), and Pacific lampreys (Entosphenus tridentatus) to determine if these unusual steroids were unique to sea lampreys or a common feature in lamprey species. In vitro production was examined through incubations of testis with tritiated precursors, and 15 alpha-T and 15 alpha-P production was confirmed in all species through co-elution with standards on both high performance liquid chromatography (HPLC) and thin layer chromatography. In vivo production was proven by demonstrating that HPLC-fractionated plasma had peaks of immunoreactive 15 alpha-T and 15 alpha-P that co-eluted with standards through using previously developed radioimmunoassays for 15 alpha-T and 15 alpha-P. The possible functionality of 15 alpha-T and 15 alpha-P was further examined in silver and Pacific lampreys by investigating the effect of injection of either type of lamprey GnRH on plasma concentrations of 15 alpha-T and 15 alpha-P. Injections with exogenous GnRH did not affect circulatory levels of either steroid in silver lampreys, and only GnRH III elicited higher levels of both steroids in Pacific lampreys. The 15 alpha-hydroxylase enzyme(s) for steroids appeared to present in adult males of all species examined, but the question of whether 15 alpha-hydroxylated steroids are functional in these lamprey species, and the significance of the 15-hydroxyl group, requires further research.     

Distinct cell types control lymphoid subset development by means of IL-15 and IL-15 receptor alpha expression

IL-15 and the IL-15 receptor (IL-15R)alpha chain are essential for normal development of naive CD8 T cells, intestinal intraepithelial lymphocytes (IEL), and natural killer (NK)/NK/T cells. However, whether IL-15R alpha expression by these subsets is necessary for their production and which cell type needs to produce IL-15 to drive development are unknown. We analyzed the requirements for IL-15 and IL-15R alpha expression by bone marrow-derived or parenchymal cells for mediating lymphocyte subset development. Naive CD8 T cell development required IL-15R alpha expression by both bone marrow-derived and parenchymal cells, whereas memory-phenotype CD8 T cells required IL-15R alpha expression only by hematopoietic cells. In contrast and surprisingly, the development of IEL subsets, particularly CD8 alpha alpha Thy1(-)V gamma 5(+) T cell antigen receptor gamma delta and the CD8 alpha alpha Thy1(-) T cell antigen receptor alpha beta IEL populations, depended completely on parenchymal cell expression of IL-15R alpha and IL-15 but not IL-15R beta. In the case of NK and NK/T cell generation and maturation, expression of IL-15 and IL-15R alpha by both parenchymal and hematopoietic cells was important, although the latter played the greatest role. These results demonstrated dichotomous mechanisms by which IL-15 regulated lymphoid development, interacting with distinct cell types depending on the developmental pathway.     

15 alpha-Hydroxytestosterone produced in vitro and in vivo in the sea lamprey,Petromyzon marinus

Prior research has shown that the testes of lampreys are able to synthesize 15-hydroxylated steroid hormones in vitro. Here we show that testes of the sea lamprey Petromyzon marinus L. are able to convert tritiated testosterone into tritiated 15alpha-hydroxytestosterone (15alpha-T) in high yield. The identity of the tritiated 15alpha-T has been confirmed by: co-elution with standard 15alpha-T on high performance liquid chromatography (HPLC); co-elution on thin layer chromatography (TLC); co-elution of acetylated tritiated and standard 15alpha-T on TLC; and strong binding to an antiserum developed against 15alpha-T. The strong reaction between the tritiated 15alpha-T and the antiserum has been used to develop a radioimmunoassay (RIA). The RIA operates over the range of 500-2pg per tube; and can be applied directly to plasma samples. This assay has been used to demonstrate that 15alpha-T is present in blood plasma of the sea lamprey. The concentrations of 15alpha-T in captive lamprey were found to be as follows (pg/ml; mean+/-SEM, n): parasitic stage (reproductively immature), <20, n=7; pre-ovulatory females, 156+/-30, n=8; ovulated females, 62+/-9, n=5; pre-spermiating males, 275+/-19, n=8; spermiating males, 216+/-48, n=8. When spermiating male plasma was fractionated on HPLC, immunoreactivity was found exclusively in the expected elution position of 15alpha-T. The biological significance of this steroid has yet to be established.     

抗凋亡因子XIAP和PED/PEA-15在前列腺癌(PC-3)中的表达及对细胞凋亡的影响

目的 检测抗凋亡因子XIAP与PED／PEA-15在前列腺癌细胞（PC-3）中的表达，探讨二者对前列腺癌细胞凋亡的影响。方法 应用半定量RT—PCR法检测前列腺癌细胞（PC-3）中PED／PEA-15和XIAP的表达。设计并构建PED／PEA-15和XIAP特异的siRNA载体，以脂质体法转染二者的siRNA载体至前列腺癌细胞（PC-3）中，半定量RT-PCR法检测特异siRNA载体对PED／PEA-15和XIAP转录的影响；光镜观察细胞形态改变；流式细胞法检测细胞凋亡的变化。结果 半定量RT-PCR显示PED／PEA-15和XIAP均在前列腺癌细胞（PC-3）中高表达。酶切和DNA测序证实XIAP和PED／PEA-15siRNA载体构建成功。共转染XIAP和PED／PEA-15siRNA载体入PC-3细胞，可导致XIAP和PED／PEA-15的转录抑制，并增加PC-3细胞对阿霉素的敏感性，凋亡明显增加，处理组凋亡率为79％，对照组为46％，两组差异有统计学意义（P〈0．05）。结论 PED／PEA-15和XIAP在前列腺癌的凋亡中可起重要作用。     

Serum and muscle interleukin-15 levels decrease in aging mice: Correlation with declines in soluble interleukin-15 receptor alpha expression

Interleukin-15 (IL-15) is a skeletal muscle-derived cytokine with favorable effects on muscle mass and body composition. Modulation of IL-15 levels has been suggested as a treatment for sarcopenia and age-associated increases in adiposity. However, it is unclear whether IL-15 levels change during aging, as measurement of IL-15 at physiological concentrations in mice has been technically difficult, and translational regulation of IL-15 is complex. Moreover, the IL-15 receptor alpha (IL-15Rα) can comprise part of a membrane-associated receptor complex, or appear as a soluble form which stabilizes IL-15 and facilitates IL-15 secretion. Here, we report measurement of physiological levels of murine IL-15, and determine that muscle and serum IL-15 levels decline progressively with age. However, expression of IL-15 mRNA and membrane-associated subunits of the IL-15 receptor did not change with age in muscle. Expression of soluble IL-15Rα (sIL-15Rα) mRNA declined 5-fold with age, and serum IL-15 levels correlated highly with muscle sIL-15 mRNA expression, suggesting declines in sIL-15Rα expression lead to decreased circulating IL-15 levels during aging. These findings complement studies which described several single-nucleotide polymorphisms in the human IL-15Rα gene which impact muscularity and adiposity, and provide a technical basis for further investigation of IL-15 and the sIL-15Rα in determining body composition in aging mice, as a model for humans.     

The reproducibility and agreement of three indices of airway responsiveness to histamine in asthmatic children

In 12 asthmatic children, aged 8-14 years, we investigated the possibility of using a provocation concentration of histamine (PC) causing a 10% or 15% fall in baseline forced expiratory volume in 1 sec (FEV1), instead of a PC20 histamine, in the assessment of bronchial hyperreactivity. Inhalation challenge tests were performed on days 6 and 7 after withdrawal of medication. PC10, PC15, and PC20 were calculated from the dose-response curves. Reproducibilities for PC10, PC15, and PC20 values for both days, determined by Student's t-test, were not significantly different. Correlation coefficients between PC20 and PC15 values on days 6 and 7 and between PC10 values on days 6 and 7 were 0.82 and 0.76, respectively; between PC20 values on day 6 and PC15 values on day 7; and between PC20 values on day 6 and PC10 values on day 7 they were 0.84 and 0.82, respectively. (P less than 0.01 for all r values). The predictive value of PC20 for PC10 and PC15 was determined by a least-squares regression line with 95% confidence intervals. Variances between PC10, PC15, and PC20 were not significantly different on either day 6 or 7. Our data show that a PC10, as well as a PC15, can be used in the assessment of the degree of bronchial hyperreactivity in children with asthma.     

Differential effects of interleukin-15 (IL-15) and IL-2 on human neutrophils: modulation of phagocytosis, cytoskeleton rearrangement, gene expression, and apoptosis by IL-15

Human neutrophils have been shown recently to express both the beta and the gamma chains of the interleukin-2 receptor (IL-2R). IL-15, a cytokine that has recently been cloned and characterized, was found to share many of the biological functions of IL-2 and is known to mediate signals through IL-2R beta and IL-2R gamma. In recent studies, we observed that IL-2 exerts few effects on various neutrophil functions, but information on IL-15-neutrophil interactions is lacking. In this study, we observed that IL-15, in contrast to IL-2, induces important morphological cell shape changes that are typical of activated neutrophils. Furthermore, phagocytosis of opsonized sheep red blood cells was significantly increased by IL-15 but not by IL-2. However, similar to IL-2, IL-15 did not modulate the oxidative burst response. Furthermore, we observed that de novo RNA synthesis is increased in neutrophils by IL-15 along with de novo protein synthesis, whereas no significant effect of IL-2 was noted. Among the different proteins that were found to be upregulated by IL-15, one was identified by microsequencing as the cytoskeletal protein actin. Finally, we found that IL-15 delays apoptosis of neutrophils more efficiently than IL-2 when evaluated by both microscopic observations and flow cytometry procedures. Furthermore, this phenomenon was dose-dependent (10 to 500 ng/mL), and, at 500 ng/mL, IL-15 delayed apoptosis as strongly as granulocyte-macrophage colony-stimulating factor. This study is the first to show that IL-15 is a significant neutrophil agonist. Moreover, in view of the differential effects of IL-15 and IL-2 on this cell type, our results support the existence of a specific IL-15R component(s) on human neutrophils.