Allograft inflammatory factor-1 defines a distinct subset of infiltrating macrophages/microglial cells in rat and human gliomas

Abstract

Allograft inflammatory factor-1 (AIF-1) is a Ca2+-binding peptide that constitutes a potential modulator of macrophage activation and function during the immune response of the brain. Peptides termed microglia response factor-1 or ionized calcium-binding adaptor molecule- have been reported to be identical with AIF-1. We have investigated the expression of AIF-1 in the rat C6 glioblastoma and 9L gliosarcoma tumor models and additionally assessed AIF- expression in a diverse range of human astrocytomas by immunohistochemistry. AIF-1 was expressed by activated microglial cells and a subset of infiltrating macrophages in areas of infiltrative tumor growth and in compact tumor areas in both rat and human gliomas. Double-labeling experiments in rats and humans characterized the nature and the functional status of AIF-1+ cells. AIF-1 expression was detected in cells expressing major histocompatibility complex class II molecules and in a subset of activated macrophages/microglial cells. All MRP-8+ cells coexpressed AIF-1. In humans, there was a strong correlation of AIF-1-expressing activated macrophages/microglial cells with tumor malignancy (P < 0.0001). These results suggest that AIF-1 defines a distinct subset of tumor-associated activated macrophages/ microglial cells.

A comparative study of ectonucleotidase and P2 receptor mRNA profiles in C6 cell line cultures and C6 ex vivo glioma model

“…Data were analysed by ANOVA, followed by Tukey's test. No significant differences were observed between groups associated with activated microglia, which, by releasing cytokines, can favour angiogenesis and invasion process in gliomas (Guo et al 2004;Deininger et al 2000). P2Y 1 has a dual role; it has been implicated in decreased cell proliferation in many cancers such as melanoma (White et al 2005) but is also involved in cell proliferation stimuli in glioma cells (Czajkowski et al 2004).…”

AIF-1 and RNASET2 Play Complementary Roles in the Innate Immune Response of Medicinal Leech

“…The allograft factor 1 (AIF-1) protein, a novel cytokine-like molecule involved in immunocyte recruitment into injured/grafted or infected tissues both in vertebrates [6, 7, 43] and invertebrates [8-10, 44], has recently been characterized in leech by our research group. Indeed, a gene showing high similarity with vertebrates’ AIF-1, named Hm Iba1/alias Hm AIF-1, has been recently characterized in the central nervous system of the medicinal leech [11].…”

“…Subsequently, several AIF-1-like factors showing high amino acid sequence conservation have been identified in other metazoans (both vertebrates [6, 7] and invertebrates [8-11]). AIF-1 expression was shown to increase significantly after transplantation, wound healing, or bacterial infections, strongly suggesting its involvement in the inflammatory response and in immune system regulation by attracting macrophages to the challenged area.…”

Allograft inflammatory factor-1 in the pathogenesis of bleomycin-induced acute lung injury

“…Allograft inflammatory factor 1 (AIF-1) is a 17-kDa Ca 2+ -binding EF-hand intracellular protein that is encoded by the HLA class III genomic region (10)(11)(12). AIF-1 was originally cloned from activated macrophages in atherosclerotic allogenic heart grafts undergoing chronic immune rejection in a rat (13).…”