Oxidative response of neutrophils to platelet-activating factor is altered during acute ruminal acidosis induced by oligofructose in heifers

Reactive oxygen species (ROS) production is one of the main mechanisms used to kill microbes during innate immune response. D-lactic acid, which is augmented during acute ruminal acidosis, reduces platelet activating factor (PAF)-induced ROS production and L-selectin shedding in bovine neutrophils in vitro. This study was conducted to investigate whether acute ruminal acidosis induced by acute oligofructose overload in heifers interferes with ROS production and L-selectin shedding in blood neutrophils. Blood neutrophils and plasma were obtained by jugular venipuncture, while ruminal samples were collected using rumenocentesis. Lactic acid from plasma and ruminal samples was measured by HPLC. PAF-induced ROS production and L-selectin shedding were measured in vitro in bovine neutrophils by a luminol chemiluminescence assay and flow cytometry, respectively. A significant increase in ruminal and plasma lactic acid was recorded in these animals. Specifically, a decrease in PAF-induced ROS production was observed 8 h after oligofructose overload, and this was sustained until 48 h post oligofructose overload. A reduction in PAF-induced L-selectin shedding was observed at 16 h and 32 h post oligofructose overload. Overall, the results indicated that neutrophil PAF responses were altered in heifers with ruminal acidosis, suggesting a potential dysfunction of the innate immune response.

NFAT regulates CSF-1 gene transcription triggered by L-selectin crosslinking

L-selectin is a member of the selectin family that play an important role both in mediating the initial capture and subsequent rolling of leukocytes along the endothelial cells. Furthermore, L-selectin can function as a signal molecule. In our previous studies, we reported that L-selectin ligation could regulate CSF-1 (colony-stimulating factor-1) gene transcription, in which AP-1 acts as a crucial transcriptional factor. Here we investigated the function of the NFAT in the CSF-1 gene transcriptional events. We found that overexpression of WT NFAT induce CSF-1 gene transcription greatly in the activated Jurkat cells. Furthermore, we found that NFAT can be recruited to the nucleus after L-selectin ligation, and the nuclear NFAT interacts with the CSF-1 promoter region to regulate CSF-1 gene transcription in the L-s electin ligation activated Jurkat cells. These results indicate that nuclear NFAT can activate CSF-1 gene transcription by connecting with the CSF-1 promoter in the signaling events induced by L-selectin ligation.

Comportamiento de la forma soluble de L-selectina en niños infectados con HIV / Behavior of soluble L-selectin in HIV infected children

La L-selectina es una molécula de adhesión responsable de la adhesión inicial de los leucocitos al endotelio. Esta molécula es liberada desde la superficie celular por clivaje proteolítico después de la activación leucocitaria. Se midieron los niveles séricos de la forma soluble de la L-selectina (sL-selectina) en 51 niños HIV(+) y en 15 controles sanos HIV(-). Estos valores se compararon con parámetros de activación inmune y de progresión de enfermedad. La concentración de sL-selectina se encontró significativamente aumentada en el grupo de pacientes HIV(+). Dichos niveles eran más altos en los pacientes con mayor inmunosupresión. Se encontró una correlación positiva entre los niveles de sL-selectina y el número relativo de LTCD8, y entre sL-selectina y los niveles de la forma soluble de la molécula de adhesión intercelular-1(sICAM-1) y la inmunoglobulina A(IgA). No se obtuvo correlación significativa entre sL-selectina y los valores de la carga viral (CV) plasmática. El aumento en los niveles de sL-selectina sería otro componente entre las múltiples alteraciones inmunológicas producidas por el HIV