Splenic leukocytes

Futami, H., Eader, L. A., Komschlies, K. L., Bull, R., Grays, M. E., Ortaldo, J. R., Young, H. A., and Wiltrout, R. H. (1991) Flavone acetic acid directly induces expression of cytokine genes in mouse splenic leukocytes but not in human peripheral blood leukocytes. Cancer Res. 51, 6596-6602. 

Mouse 28 d (Swiss- 7 d/wk Webster) 24 hr/d 1.6 (decreased spleen and thymus weight, decreased leukocyte count, decrease in antibody titer following intraperitoneal immunization decreased splenic antibody forming cells) Hillam and Ozkan 1986 Pb(N03)2... 

Decreases in hemoglobin concentration and increases in erythrocyte, white blood cell, and polymorphonuclear leukocyte concentrations were noted in mice after acute dermal exposure to kerosene. A decrease in the splenic relative weight, which was not accompanied by histopathological changes, was also noted (Upreti et al. 1989). Oral exposure to JP-5 increased hematocrit levels, decreased white blood cell counts, and increased erythrocyte counts in rats (Parker et al. 1981). However, inhalation of diesel fuel aerosol induced decreases in the mean red blood cell count in rats and had no effect on white blood cells (Dalbey et al. 1987). 

The various organs of the immune system such as spleen, lymph nodes, thymus and bone marrow containing the cells involved in the various immune responses offer the possibility to harvest these cells and perform in vitro assays for evaluation of effects on the immune system. When part of an in vivo animal study this may indicate a direct toxic effect of pharmaceuticals, that is, immunosuppression (Table 18.2). So, it is feasible to obtain cell suspensions for further evaluation such as determination of cellular subsets of T and B leukocytes by fluorescent activated cell sorter analysis (FACS analysis), and determination of natural killer (NK) cell activity of the spleen cell population. An advantage of this approach is that it may lead to identification of a biomarker to be used in clinical studies. In addition, in vitro stimulation of spleen cells with mitogens activating specific subsets may indicate potential effects on the functionality of splenic cell populations. Concanavalin A (Con A) and phytohemagglutinin (PHA) activate Tcells, while lipopolysaccharide (LPS) activates primarily B cell populations. Blood is collected for total white blood cell (WBC) determination and blood cell differential count. In addition, serum can be obtained for determination of serum immunoglobulins. 

Karrow NA, Guo TL, Declos KB, Newboid RR, Weis C, Germolec DR, White KL Jr, McCay JA. Nonylphenol alters the activity of splenic NK cells and the number of leukocyte subpopulations in Sprague-Dawley rats a two generation feeding study. Toxicology 2004 196 237-245. 

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