Environmental chemical-induced macrophage dysfunction.

Abstract

Immunomodulation by environmental chemical contaminants and the role immune parameters play in toxicity and risk assessment studies is of increasing concern. Although considerable evidence has indicated that various xenobiotics may be immunosuppressive, little attention has been directed toward ascertaining a specific cellular locus which could be responsible for the impaired immune responsiveness. Since previous studies had suggested a macrophage defect in xenobiotic-induced immunosuppression and since macrophages are integral components of an immune response, an in-depth evaluation of macrophage function was conducted in xenobiotic-exposed mice. Macrophages isolated from mice receiving PCB, HCB, and dieldrin had no alteration in their in vitro O2 consumption while at rest or during phagocytosis. In addition, no alteration in in vitro phagocytic activity, phagocytic capacity or microbicidal activity was demonstrated. However, a significant impairment in the in vivo phagocytic clearance of a labelled antigen and an altered tissue distribution of the antigen was observed and was, perhaps, related, in part, to a significant decrease in serum fibronectin, an opsonic alpha 2 surface-binding glycoprotein. Furthermore, animals exposed to HCB and dieldrin, but not to PCB, had a profound decrease in their resistance to a challenge tumor cell implant which was related to a select alteration in tumor cell killing. The adherent spleen cells from HCB-treated mice had a profound suppression in their tumoricidal activity which was in contrast to dieldrin-treated mice, where the target cell type appeared to be the nonadherent cells. However, although dieldrin-exposed adherent cells (macrophages ?) did nt appear to have an altered tumoricidal capacity, all four macrophage types isolated from dieldrin-treated mice had a significantly impaired ability to process a cellular antigen. Splenic and alveolar macrophages appeared to be the most sensitive cell types to dieldrin. The present studies suggest that macrophage dysfunction may be an integral part of xenobiotic-induced immunosuppression and that the effector but not affector component of macrophage function may be the site of alteration.

Non-Coplanar PCB-Mediated Modulation of Human Leukocyte Phagocytosis: A New Mechanism for Immunotoxicity

“…Neither mouse neutrophils nor monocytes (Levin et al, 2005) were affected by the same OCs mixtures as those tested in the present study, which is not surprising in view of the lack of effects of OC on phagocytosis in several in vivo studies in mice (Loose et al, 1981) and rats (Blakley et al, 1998;Omara et al, 1998). This is of concern, as rodents are still the preferred model to assess toxicity for use in risk assessment for humans in which the effects of OCs on phagocytosis have been demonstrated in this and other studies (Hermanowicz et al, 1982;Pelletier et al, 2001;.…”

“…Macrophage and polymorphonuclear (PMN) phagocytosis was not altered by Aroclor 1242 or hexachlorobenzene (HCB) following dietary administration lasting up to 18 wk in male BALB/c mice (Loose et al, 1981). Cynomolgus monkeys fed toxaphene for 52 wk did not significantly change the phagocytic activity of peripheral blood monocytes or granulocytes (Tryphonas et al, 2000).…”

Integrated Laboratory and Field Investigations: Assessing Contaminant Risk to American Badgers

“…It is, however, possible for badgers to be exposed to CDV without mortality if adequate antibody can be produced rapidly to defeat the challenge. In order to survive CDV, badgers cannot be substantially affected by immunosuppressive contaminants such as dieldrin (Bernier et al 1987, Krzystyniak et al 1985, Loose et al 1981). One male badger had no antibody titer to CDV when captured in 1994.…”

Testing guidelines for evaluation of the immunotoxic potential of direct food additives

“…47 "* 9 The assays measure the ability of the cell to ingest a particulate substance, such as plastic beads or iron fillings. Other assay variations measure phagocytotic ability as well as the capacity of the cell to destroy various target cells (such as bacteria) through lysosomal enzyme activity.…”