Allograft inflammatory factor-1/Ionized calcium-binding adapter molecule 1 is specifically expressed by most subpopulations of macrophages and spermatids in testis

Abstract

Ionized calcium-binding adapter molecule 1 (Iba1) is a 147-amino-acid calcium-binding protein widely in use as a marker for microglia. It has actin-crosslinking activity and is involved in aspects of motility-associated rearrangement of the actin cytoskeleton. The Iba1 gene and protein are identical to allograft inflammatory factor-1 (AIF-1), a protein involved in various aspects of inflammation, which was investigated independently from Iba1. Although regarded to be monocyte/macrophage-specific, expression by germ cells in testis showed that AIF-1/Iba1 is not exclusively expressed by cells of the monocyte/macrophage lineage. Furthermore, AIF-1 was found in cells not belonging to the monocyte/macrophage lineage under pathological conditions. Here, the distribution of AIF-1/Iba1 in the normal mouse has been examined, by immunohistochemistry, to determine whether AIF-1/Iba1 expression is confined to macrophages and spermatids. Spermatids are the only cells not belonging to the monocyte/macrophage lineage found to express AIF-1/Iba1 in the normal mouse, by this method. This study has not demonstrated AIF-1/Iba1 expression in dendritic cells, although this protein might be expressed by subsets of dendritic cells. AIF-1/Iba1 can be regarded a "pan-macrophage marker" because, except for alveolar macrophages, all subpopulations of macrophages examined express AIF-1/Iba1.

Yolk-sac–derived macrophages regulate fetal testis vascularization and morphogenesis

“…At E11.5, F4/80-and Cx3cr1-GFP-expressing cells near the gonad border increased in number and also expressed CSF1R and the microglial/macrophage marker ionized calcium binding adaptor molecule 1 (IBA1) (also called "AIF1") (27,28) (Fig. 1 E and F), consistent with a macrophage identity.…”

Identification of an Epitope from Adenine Nucleotide Translocator 1 That Induces Inflammation in Heart in A/J Mice

“…31 Groups of mice were immunized with or without ANT 1 [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40], and the animals were subjected for MRM imaging to measure end diastolic volume, end systolic volume, SV, EF, and left ventricular wall thickness. Expectedly, both SV and EF were significantly reduced in immunized animals on different days as compared to healthy group [day 30 to 35: SV, 11.33 AE 2.17 mL versus 25.67 AE 4.67 mL; EF, 30.17 AE 2.52% versus 65.67 AE 0.88% (P < 0.05); and day 46: SV, 9.00 AE 2.52 mL versus 29.00 AE 0.58 mL; EF, 24.00 AE 4.51% versus 60.00 AE 1.15% (P < 0.01)].…”

“…The presence of such a repertoire of cells has previously shown to be correlated with the lack of expression of autoantigens, like cardiac myosin and proteolipid protein in the thymus. 43,44 Splenocytes harvested from naïve mice were used to assess their reactivity to ANT 1 [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40]. Using RNase 43-56 as a control peptide, we noted that the splenocytes did not respond to ANT 1 21-40 (Supplemental Figure S2), suggesting the absence of preexisting endogenously derived repertoire of ANT-reactive T cells in the naïve animals.…”

“…In addition, by using AST as a biochemical readout of liver damage, we noted that serum from animals immunized with ANT 1 [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] showed elevated AST levels during the chronic phase of disease (beyond 30 days after immunization) as compared to naïve mice (Supplemental Figure S4). However, livers, but not brains, from animals that received CFA/PT with no peptide also showed relatively more inflammatory foci as compared to ANT 1 21-40eimmunized group (34.93 AE 2.82 versus 20.86 AE 3.58; P Z 0.039) ( Figure 7 and Table 4), suggesting that the occurrence of inflammation in livers from the ANT 1 21-40 group is not specific to antigen.…”

“…One such model for cardiac autoimmunity is experimental autoimmune myocarditis (EAM), which involves induction of disease in susceptible rodent strains by immunizing animals with cardiac antigens or their peptide fragments. 23e25 In this study, we used the EAM model in A/J mice to demonstrate that ANT 1 possesses multiple immunodominant epitopes, and one of these, ANT 1 [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40], was found to induce myocarditis in the immunized animals. Furthermore, myocarditogenicity of ANT 1 [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] was associated with the generation of T cells capable of producing predominantly IL-17A, and the antigen-sensitized T cells can transfer the disease to naïve recipients, suggesting that ANT 1 can be a potential autoantigen in the heart autoimmunity.…”