Activation of Tumor-Associated Macrophages by Thymosin Alpha-1

Abstract

It was shown earlier that the progressive growth of a transplantable T-cell lymphoma of spontaneous origin, designated as Dalton's lymphoma (DL), in a murine host is associated with an inhibition of macrophages (TAM) along with an involution of thymus. However, it remained unclear if a decline in the level of thymic peptides in DL-bearing host, due to thymic regression, has any implications in the inhibited responses of TAM. Therefore, the present investigation was under taken to study whether the TAM of DL-bearing host can be activated to tumoricidal state by peptides of thymic origin. It was observed that intraperitoneal administration of thymosin alpha 1 to DL-bearing mice resulted in activation of TAM. Such TAM were found to produce enhanced amount of interleukin-1 (IL-1), tumor necrosis factor (TNF), reactive oxygen intermediates (ROI), nitric oxide (NO) and showed an increased abilities of pinocytosis, phagocytosis, antigen presentation and tumor cytotoxicity. The TAM were found to be directly responsive to thymosin alpha1 as in vitro treatment with thymosin alpha 1 could activate TAM to tumoricidal state. Treatment of TAM with thymosin alpha 1 also enhanced their LPS responsiveness for an augmented state of activation. The findings of this study demonstrate for the first time that the TAM of a T cell lymphoma can be activated to tumoricidal state by thymosin alpha 1.

Thymosin α₁ Activates Complement Receptor-Mediated Phagocytosis in Human Monocyte-Derived Macrophages

“…This effect was associated with a significant augmentation in the number of circulating polymorphonuclear cells (PMNs) and of their candidacidal activity, although the issue of whether the effect of Tα1 on PMNs was a direct one on PMN precursor cells or mediated by other cell populations, such as lymphocytes or monocytes, remained unresolved at that time [21]. Studies by other groups of investigators also focused on the protective activity of Tα1 against opportunistic infections in animal models [22] and, more generally, on the capacity of Tα1 to potentiate several murine as well as human macrophage abilities [23,24,25]. Tα1 is able to upregulate the expression of the major histocompatibility complex class I in murine and human tumor cell lines and in primary cultures of human monocyte-enriched peripheral blood mononuclear cells (PBMCs) [26].…”

Immunopotentiating effect of proton pump inhibitor pantoprazole in a lymphoma-bearing murine host: Implication in antitumor activation of tumor-associated macrophages

“…Phagocytic activity of TAM was carried out as described earlier [22]. TAM grown on glass coverslips were incubated with heatkilled yeast cells (2 × 10 8 /ml) for 90 min at 37 • C in a CO 2 incubator.…”

“…As hematological malignancies are considered as one of the most complicated malignancies for clinical management [16,17], we have been studying various aspects of host-tumor relationship in a murine model of a transplantable T cell lymphoma of spontaneous origin designated as Dalton's lymphoma (DL) [18][19][20][21][22][23][24][25]. We have also shown that TAM of a DL-bearing host are in a suppressed state and resistant to signals of activation [26,27].…”

Suppression of macrophage function in AK-5 tumor transplanted animals: role of TGF-β1

“…NO released from activated macrophages suppressed the proliferation of tumor cells [12]. Coculture of macrophages and tumor cells leads to increased production of NO by the macrophages with concomitant cytotoxicity against the tumor cells [13]. TGF-␤1, suppresses the production of both superoxide [14] and NO by IFN-␥-induced macrophages [15].…”