Macrophage phenotype/function can be modulated by various T-cell lymphokines (LK). The alteration of macrophage phenotype is a result of LK concentration, duration of exposure, and the level of macrophage activation when obtained from in vivo sources through elicitation by either sterile irritants or immune cellular mechanisms. In order to dissect macrophage activation into discrete signals T cell hybridomas were constructed by fusing HAT sensitive BW5147 cells with nylon-wool purified, con A stimulated T cells. The resulting T cell hybrids were screened for their ability to: (a) protect macrophages from the cytopathic effect of Naegleria; (b) induce class II MHC gene product (Ia antigen) expression; (c) increase cytostasis and tumoricidal activity; and (d) alter ectoenzyme profiles on either resident or thioglycollate (TG) elicited macrophages. Two hybridomas (T-3 and T-9) were selected for further evaluation because of their activity patterns. Supernatants from T-3 and T-9 were compared with cloned Y-interferon (γ-IFN) for alteration of biological activities. Both T-3 and T-9 were able to protect resident macrophage cells from Naegleria but had no protective effect on TG-macrophages. T-9 supernatant had patterns of activity similar to γ-IFN while T-3 patterns were different. The addition of anti-Y-IFN removed T-9 cytostatic activity while not affecting T-3 induced activity. The LK inducing protection from the cytopathic effect of Naegleria lysate is not γ-IFN but another molecular moiety. It was also shown that γ-IFN does not protect TG-macrophages from the destructive effects of adenylate cyclase produced by Bordetella pertussis. We conclude that activation of macrophages for the destruction of tumor cells and activation for protection against amoeba and bacteria occur via different biological pathways. Furthermore, we have proposed an association between the cell cycle and the responsiveness of resident and TG-elicited macrophages to specific LK.
| Identifer | oai:union.ndltd.org:vcu.edu/oai:scholarscompass.vcu.edu:etd-5634 |
| Date | 01 January 1985 |
| Creators | Futch, William S., Jr. |
| Publisher | VCU Scholars Compass |
| Source Sets | Virginia Commonwealth University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Theses and Dissertations |
| Rights | © The Author |
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