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Sialoadhesin (CD169/Siglec-1, Sn) is a macrophage receptor that interacts with sialic acids on both host cells and pathogens. It is a type 1 membrane protein with an unusually large number of 17 extracellular immunoglobulin (Ig)-like domains, made up of an N-terminal V-set domain that binds sialic acid and 16 adjacent C2-set domains. The potential importance of 17 Ig domains in Sn for mediating cellular interactions has not been investigated experimentally. In the present study, Chinese Hamster Ovary (CHO) cells were stably transfected with full-length or truncated forms of Sn. Using human red blood cells (RBC) as a model system, CHO cells expressing truncated forms of Sn with 4 or less Ig domains were unable to bind RBC in comparison to the full-length protein. Immunoelectron microscopy of the CHO cells indicated that full-length Sn extends ~ 33 nm from the plasma membrane compared with ~ 14 nm for a truncated form with 6 N-terminal Ig domains. Co-expresssion of Sn-expressing CHO cells with heavily glycosylated membrane proteins of differing predicted lengths resulted in selective modulation of Sn-dependent binding to RBC and supported the hypothesis that Sn has evolved 17 Ig domains to escape inhibitory cis-interactions. The functional significance of the extended length of Sn was demonstrated in experiments with macrophages showing that Sn synergizes with phagocytic receptors FcR and TIM-4 to strongly promote uptake of IgG-opsonized and eryptotic RBC respectively., (© 2023. The Author(s).)

Olfactomedin-4 (OLFM4) is an olfactomedin-domain-containing glycoprotein, which regulates cell adhesion, proliferation, gastrointestinal inflammation, innate immunity and cancer metastasis. In the present study we investigated its role in skin regeneration. We found that OLFM4 expression is transiently upregulated in the proliferative phase of cutaneous wound healing in humans as well as in mice. Moreover, a significant increase in OLFM4 expression was detected in the skin of lesional psoriasis, a chronic inflammatory disease characterized by keratinocyte hyperproliferation. In vitro experiments demonstrated that OLFM4 selectively stimulated keratinocyte proliferation and increased both keratinocyte and fibroblast migration. Using proteotranscriptomic pathway analysis we revealed that transcription factors POU5F1/OCT4 and ESR1 acted as hubs for OLFM4-induced signalling in keratinocytes. In vivo experiments utilizing mouse splinted full-thickness cutaneous wound healing model showed that application of recombinant OLFM4 protein can significantly improve wound healing efficacy. Taken together, our results suggest that OLFM4 acts as a transiently upregulated inflammatory signal that promotes wound healing by regulating both dermal and epidermal cell compartments of the skin., (© 2022. The Author(s).)

The immune system is tightly regulated to maintain an appropriate balance between immune activation and tolerance. Macrophages play a key role in this process since they express many pathogen recognition molecules as well as receptors for 'self'. Sialoadhesin is a major macrophage receptor that specifically recognizes sialic acid, an abundant component of host glycoconjugates but which can also be found on several human pathogens. In recent years, several studies have demonstrated that sialoadhesin can contribute to the uptake and processing of sialylated pathogens as well as playing an important role in regulating inflammatory and autoimmune responses via recognition of self.