Biomedical subjects

M C Ruzek

Publications and source records attributed to M C Ruzek.

5 recordsLinked to original sources

PubMed1996

A combination of IL-10 and direct contact with plasma cell tumors decreases CD23 expression on splenic B cells.

We and others have previously found that splenic B cells from plasma cell tumor-bearing mice exhibit decreased CD23 expression. In the present study we further examined the mechanism of CD23 down-regulation by plasma cell tumors. We show here that although direct contact is required between the tumor cells and B cells, it is not sufficient, since fixed tumor cells do not induce the same reduction in CD23 expression. We have identified IL-10, a cytokine produce by the tumors, as the sole soluble factor that contributes to decreased CD23 expression on B cells induced by plasma cell tumors because 1) Abs to IL-10 prevent the loss of CD23 induced by plasma cell tumors both in vitro and in vivo; 2) engineered IL-10 negative variants of these tumors are reduced in their ability to down-regulate CD23 expression; 3) rIL-10 alone induces partial, but significant, decreases in CD23 expression on normal splenic B cells; and 4) the addition of IL-10 and fixed tumor cells to cultures of normal splenocytes decreases CD23 expression to levels similar to those in cocultures with live tumor cells. Collectively, these results demonstrate that plasma cell tumors down-regulate CD23 expression on B cells by a coordinate mechanism of IL-10 plus contact-mediated events and reveal a novel role for IL-10 in the regulation of CD23 expression on B cells that is suggestive of host B cell activation in the presence of the tumor.

Animals↗

PubMed1996

In vitro and in vivo recovery of IFN-gamma, but not IL-2, production by IL-12 in mice with plasma cell tumors.

We have previously found that T cells from mice bearing plasma cell tumors (PCT mice) demonstrate decreased proliferation as well as decreased production of the Th 1-associated cytokines IL-2 and IFN-gamma in response to polyclonal stimulation. In the present study, we have examined soluble factors as possible elements required to rescue this decreased proliferation and cytokine production by splenocytes from PCT mice. We find that the addition of supernatants from stimulated normal splenocytes has no effect on proliferation of IL-2 production by splenocytes from PCT mice. In contrast, these supernatants completely restore IFN-gamma production by splenocytes from PCT mice. We have found that IL-12 is responsible for the observed increase in IFN-gamma production because: (i) addition of anti-IL-12 antibody blocks this recovery of IFN-gamma production by these supernatants, (ii) the addition of recombinant IL-12 to cultures of splenocytes from PCT mice results in increased IFN-gamma production and (iii) in vivo treatment of PCT mice in IL-12 also results in increased IFN-gamma production by the subsequently activated splenocytes, but has little effect on proliferation or IL-2 production. These results demonstrate that both in vitro and in vivo, IL-12 selectively restores the decreased production of IFN-gamma by splenocytes from PCT mice.

Animals↗

PubMed1995

Plasma cells tumors decrease CD23 mRNA expression in vivo in murine splenic B cells.

CD23, the low-affinity Fc receptor for IgE, is constitutively expressed on mature, naive B cells, but is lost following B cell activation. We and others have shown that CD23 expression on B cells decreases in mice bearing plasma cell tumors. In contrast to these findings, we find that IgE-secreting tumors do not cause a loss of CD23 expression on host splenic B cells. Decreased expression of CD23 on B cells induced by plasma cell tumors requires direct contact between tumor cells and B cells; and other host cells are not involved. The loss of surface CD23 expression is associated with a decrease in steady-state CD23 mRNA levels in B cells from plasma cell tumor-bearing mice. Interestingly, loss of CD23 mRNA is observed even in B cells from mice with IgE-secreting tumors, where we find surface CD23 protein expression to be similar to that of normal mice. The maintenance of surface CD23 expression on B cells in mice with IgE-secreting tumors is dependent solely on the presence of IgE, and is not a tumor-specific effect. Therefore, we conclude that in vivo, IgE secreted by plasma cell tumors can result in the maintenance of normal levels of surface CD23 expression by a post-transcriptional mechanism, even when the tumor induces a down-regulation of CD23 mRNA levels.

Animals↗

PubMed1995

Specific decrease of Th1-like activity in mice with plasma cell tumors.

Previously we examined the ability of the host's immune responses to regulate Ig production in an IgE-secreting murine plasma cell tumor (B53). In the present study we have examined the reverse phenomenon, in that we have investigated the effects of this and other plasma cell tumors on the immune responses of their hosts. We found that splenocytes from plasma cell tumor-bearing mice demonstrate decreased proliferation in response to polyclonal stimulation by either Con A or a combination of PMA and calcium ionophore (A23187). Fractionation of the splenocytes demonstrated that this reduction in proliferation was confined to CD4+ T cells and that the proliferation of CD8+ T cells was unaffected. In order to determine whether the down-modulatory effects of the tumor were confined to a particular CD4+ helper T cell subset, we examined the production of cytokines representing the Th1 subset (IL-2 and IFN-gamma) and the Th2 subset (IL-4 and IL-10) from stimulated splenocytes and from stimulated enriched splenic T cells. We found that both stimulated splenocytes and T cells from plasma cell tumor-bearing mice produced lower levels of the Th1 cytokines IL-2 and IFN-gamma compared with normal cultures, demonstrating that Th1-like responses are inhibited in the hosts of these tumors. However, no alterations in the production of the Th2 cytokines IL-4 and IL-10 were observed in these stimulated splenocyte or T cell cultures from the tumor-bearing mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Metabolism of 2-aminofluorene by human polymorphonuclear leukocytes: more evidence for the association between inflammation and cancer.

Recent investigations have demonstrated the ability of leukocytes to metabolize promutagens or procarcinogens into their genotoxic forms. As a possible explanation for the association between inflammation and cancer, we and others have hypothesized that local accumulations of leukocytes could take up nearby promutagens, metabolize them, and release genotoxic agents that may cause damage in the surrounding tissue. Using a modified, two-step preincubation protocol with Salmonella, we have tested this hypothesis. We have shown that total human peripheral blood leukocytes, cultured in the presence of 2-aminofluorene for 18 hr, can metabolize 2-aminofluorene into agents mutagenic to Salmonella typhimurium strain TA98. Furthermore, experiments in which polymorphonuclear leukocytes were separated from mononuclear leukocytes demonstrated that the PMNs metabolized 2-aminofluorene to a much greater extent than the MNs.

Fluorenes↗