Hyper-Activated Pro-Inflammatory CD16+ Monocytes Correlate with the Severity of Liver Injury and Fibrosis in Patients with Chronic Hepatitis B

BACKGROUND: Extensive mononuclear cell infiltration is strongly correlated with liver damage in patients with chronic hepatitis B virus (CHB) infection. Macrophages and infiltrating monocytes also participate in the development of liver damage and fibrosis in animal models. However, little is known regarding the immunopathogenic role of peripheral blood monocytes and intrahepatic macrophages. METHODOLOGY/PRINCIPAL FINDINGS: The frequencies, phenotypes, and functions of peripheral blood and intrahepatic monocyte/macrophage subsets were analyzed in 110 HBeAg positive CHB patients, including 32 immune tolerant (IT) carriers and 78 immune activated (IA) patients. Liver biopsies from 20 IA patients undergoing diagnosis were collected for immunohistochemical analysis. IA patients displayed significant increases in peripheral blood monocytes and intrahepatic macrophages as well as CD16(+) subsets, which were closely associated with serum alanine aminotransferase (ALT) levels and the liver histological activity index (HAI) scores. In addition, the increased CD16(+) monocytes/macrophages expressed higher levels of the activation marker HLA-DR compared with CD16(-) monocytes/macrophages. Furthermore, peripheral blood CD16(+) monocytes preferentially released inflammatory cytokines and hold higher potency in inducing the expansion of Th17 cells. Of note, hepatic neutrophils also positively correlated with HAI scores. CONCLUSIONS: These distinct properties of monocyte/macrophage subpopulations participate in fostering the inflammatory microenvironment and liver damage in CHB patients and further represent a collaborative scenario among different cell types contributing to the pathogenesis of HBV-induced liver disease

Soft Gluon Approach for Diffractive Photoproduction of J/psi

We study diffractive photoproduction of $J/\psi$ by taking the charm quark as a heavy quark. A description of nonperturbative effect related to $J/\psi$ can be made by using NRQCD. In the forward region of the kinematics, the interaction between the $c\bar c$-pair and the initial hadron is due to exchange of soft gluons. The effect of the exchange can be studied by using the expansion in the inverse of the quark mass $m_c$. At the leading order we find that the nonperturbative effect related to the initial hadron is represented by a matrix element of field strength operators, which are separated in the moving direction of $J/\psi$ in the space-time. The S-matrix element is then obtained without using perturbative QCD and the results are not based on any model. Corrections to the results can be systematically added. Keeping the dominant contribution of the S-matrix element in the large energy limit we find that the imaginary part of the S-matrix element is related to the gluon distribution for $x\to 0$ with a reasonable assumption, the real part can be obtained with another approximation or with dispersion relation. Our approach is different than previous approaches and also our results are different than those in these approaches. The differences are discussed in detail. A comparison with experiment is also made and a qualitative agreement is found.Comment: 25 pages, 6 figures. Tiny changes in two figures, conclusion and text unchanged, accpeted by Nucl. Phys.