Pediatr Allergy Respir Dis.  2006 Sep;16(3):197-205.

Functions of Siglecs in Allergic Inflammation

• Lee HH

Abstract

Siglecs are sialic acid binding Ig-like lectins, subset of the immunoglobulin superfamily. They are characterized by a homologous N-terminal V-set Ig-like domain and C2 set Ig-like domains. N-terminal domains have sialic acid binding activity. In humans, 11 Siglecs have been described sialoadhesin(Siglec-1), CD22(Siglec-2), CD33(Siglec-3), MAG(Siglec-4), more recently described CD33-related Siglecs(Siglec 5-11). Siglecs express most signal via immunoreceptor tyrosine-based inhibition motif(ITIM) cytoplasmic domains. The cytoplasmic tails of all Siglecs except sialoadhesin have one or more tyrosine residues within potential signaling motifs. Inhibitory function of other Siglecs such as Siglec-7 or Siglec-9 was shown in RBL-2H3 cells. Co-crosslinking of Siglec-7 or Siglec-9 and Fc epsilon R1 substantially reduced the serotonin release of RBL-7 and RBL-9 cells. Siglec-8 is expressed on human eosinophils, mast cells and basophils. Siglec-8 has two tyrosine motifs, a proximal motif and a distal motif. They have some inhibitory functions in immune system. We have observed that Siglec-8 is able to inhibit the IgE receptor-mediated beta-hexosaminidase release of RBL-2H3 cells following co-crosslinking. Co-crosslinking of Siglec-8 and Fc epsilon R1 reduced the hexosaminidase release of RBL-2H3 cells. These results show that Siglec-8 is as potent as Siglec-7 and Siglec-9 in delivering inhibitory signals to RBL-2H3 cells. Siglec-8 should be a new member of the inhibitory receptor superfamily and the membrane-proximal ITIM is essential for the inhibitory function of Siglec-8 molecules. Although these molecules present specific marker for the allergic cell types, more work is needed to understand the signaling mechanism and the role in various disease processes.

Keyword

Siglecs; Lectins; Immunoglobulin superfamily; ITIM

MeSH Terms

Basophils
beta-N-Acetylhexosaminidases
Cytoplasm
Eosinophils
Hexosaminidases
Humans
Immune System
Immunoglobulin E
Immunoglobulins
Inflammation*
Lectins
Mast Cells
N-Acetylneuraminic Acid
Serotonin
Sialic Acid Binding Ig-like Lectin 1
Sialic Acid Binding Immunoglobulin-like Lectins*
Tyrosine
Hexosaminidases
Immunoglobulin E
Immunoglobulins
Lectins
N-Acetylneuraminic Acid
Serotonin
Sialic Acid Binding Ig-like Lectin 1
Sialic Acid Binding Immunoglobulin-like Lectins
Tyrosine
beta-N-Acetylhexosaminidases