Augmentation of Organ-Associated NK Activity by BRMs: Association of NK Activity with Mononuclear Cell Infiltration

Liver-associated large granular lymphocytes: Morphological and functional aspects.

“…One is the increase in the number of LGLs, and the other is the induction of "activated" LGLs by BRMs. Histologically, in a BRM-treated liver, infiltration of mononuclear cells is observed (WILTROUT et al, 1986). The number of LGLs shows a 10 to 50-fold increase in mice (WILTROUT et al, 1984) and a 4 to 6-fold increase in rats (BOUWENS and WISSE, 1988).…”

Regulation and antimetastatic functions of liver-associated natural killer cells

“…What is clear is that some viral infections or exogenously administered biological agents can modulate the number and function of these lymphocyte subsets in the liver. Early studies from our laboratory demonstrated that the administration of a variety of biological agents induced a rapid increase in the number of cells with LGL morphology and cytotoxic activity against NKsensitive targets ( Table 2) (17,(43)(44)(45). Subsequent studies showed that much of this ability to recruit/activate NK cells was likely a result of the propensity of these agents to induce the production of cytokines, since interferons and interleukins were also shown to induce similar increases in the number and function of liver-associated NK cells (18).…”

“…Because there is a resident population of NK cells in normal liver (25,26,39), and liver-associated NK cells can proliferate in response to viral infections (7,8,10), it is likely that at least some of the increase in NK-cell number and function that occurs in the liver after administration of biological response modifiers is due to proliferation of NK cells. However, a considerable portion of the augmented NK activity observed after initiation of viral infections or the administration of immune modifiers is due to the active recruitment of NK cells to the liver (7,45). In particular, it has been shown that the selective ablation of bone marrow cellularity by the administration of the bone-seeking isotope strontium 89 ( 89 Sr) inhibits the ability of a variety of immune modifiers to increase the number and function of NK cells in the liver (46).…”

“…The signals that regulate these molecules may differ based on the nature of the overall infectious or inflammatory stimulus. For example, early studies from our laboratory showed that polyribonucleotides and some other biological agents induced a variety of cytokines, including TNF-a and IFN-a/b, in concert with an accumulation of NK cells in the liver (44,45). Later studies demonstrated that TNF-a enhanced the binding of NK cells to endothelial cells in vitro, and antibodies specific for TNF-a inhibited the ability of polyinosinic-polycytidylic acid stabilized in carboxymethylcellulose (poly-ICLC) to recruit NK cells into the liver (Fig.…”