Homolog of allograft inflammatory factor-1 induces macrophage migration during innate immune response in leech

• Published in: Cell and tissue research Vol. 359; no. 3; pp. 853 - 864
• Main Authors: Schorn, Tilo, Drago, Francesco, Tettamanti, Gianluca, Valvassori, Roberto, de Eguileor, Magda, Vizioli, Jacopo, Grimaldi, Annalisa
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.03.2015; Springer Berlin Heidelberg; Springer; Springer Nature B.V; Springer Verlag
• Subjects: adhesion; allografting; Analysis; angiogenesis; Animals; Antibodies - pharmacology; Biomarkers - metabolism; Biomedical and Life Sciences; Biomedicine; Blotting, Western; Cell Movement - drug effects; Cell Movement - immunology; Cell Shape - drug effects; Cellular biology; central nervous system; chemoattractants; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - pharmacology; expressed sequence tags; genes; glycoproteins; Hirudinea; Hirudo; Hirudo medicinalis; Hirudo medicinalis - cytology; Hirudo medicinalis - immunology; Hirudo medicinalis - microbiology; Hirudo medicinalis - ultrastructure; Human Genetics; Immune response; Immune system; Immunity, Innate - drug effects; Immunohistochemistry; inflammation; innate immunity; Integrins; integument; invertebrates; Leukocyte Common Antigens - metabolism; Life Sciences; Macrophages; Macrophages - cytology; Macrophages - drug effects; Macrophages - immunology; Molecular Medicine; pathogens; polyclonal antibodies; Protein binding; Protein expression; Proteomics; Recombinant proteins; Recombinant Proteins - pharmacology; Regular Article; Sequence Homology, Amino Acid; Transplantation of organs, tissues, etc; vertebrates; Worms; AIF-1; Macrophage-like cells; Innate immune response
• ISSN: 0302-766X; 1432-0878
• DOI: 10.1007/s00441-014-2058-7

Allograft inflammatory factor-1 (AIF-1) is a 17-kDa cytokine-inducible calcium-binding protein that, in vertebrates, plays an important role in the allograft immune response. Its expression is mostly limited to the monocyte/macrophage lineage. Until recently, AIF-1 was assumed to be a novel molecule involved in inflammatory responses. To clarify this aspect, we have investigated the expression of AIF-1 after bacterial challenge and its potential role in regulating the innate immune response in an invertebrate model, the medicinal leech (Hirudo medicinalis). Analysis of an expressed sequence tag library from the central nervous system of Hirudo revealed the presence of the gene Hmaif-1/alias Hmiba1, showing high homology with vertebrate aif-1. Immunohistochemistry with an anti-HmAIF-1 polyclonal antibody revealed the constitutive presence of this protein in spread CD68⁺macrophage-like cells. A few hours after pathogen (bacterial) injection into the body wall, the amount of these immunopositive cells co-expressing HmAIF-1 and the common leucocyte marker CD45 increased at the injected site. Moreover, the recombinant protein HmAIF-1 induced massive angiogenesis and was a potent chemoattractant for macrophages. Following rHmAIF-1 stimulation, macrophage-like cells co-expressed the macrophage marker CD68 and the surface glycoprotein CD45, which, in vertebrates, seems to have a role in the integrin-mediated adhesion of macrophages and in the regulation of the functional responsiveness of cells to chemoattractants. CD45 is therefore probably involved in leech macrophage-like cell activation and migration towards an inflammation site. We have also examined its potential effect on HmAIF-1-induced signalling.