Siamon Gordon

Sialoadhesin, a macrophage sialic acid binding receptor for haemopoietic cells with 17 immunoglobulin-like domains

Sialoadhesin is a macrophage‐restricted adhesion molecule of 185 kDa that mediates sialic acid‐dependent binding to cells. It is expressed strongly by macrophages in lymphoid and haemopoietic tissues where it is likely to mediate cell‐cell interactions. Here we report the molecular cloning of murine sialoadhesin and show that it is a new member of the immunoglobulin (Ig) superfamily with 17 Ig‐like domains. COS cells transfected with a cDNA encoding full‐length sialoadhesin bound mouse bone marrow cells in a sialic acid‐dependent manner. Alternatively spliced cDNAs, predicting soluble forms of sialoadhesin containing the first three or 16 Ig‐like domains of sialoadhesin, were expressed in COS cells and the respective proteins purified. When immobilized on plastic, the 16‐domain form bound cells in a sialic acid‐dependent manner, suggesting that sialoadhesin can function in both secreted and membrane‐bound forms. The most similar proteins in the database were CD22, myelin‐associated glycoprotein, Schwann cell myelin protein and CD33. Like sialoadhesin, CD22 mediates sialic acid‐dependent cell adhesion. The sequence similarity of sialoadhesin to CD22 and related members of the Ig superfamily indicates the existence of a novel family of sialic acid binding proteins involved in cell‐cell interactions.

Membrane Molecules as Differentiation Antigens of Murine Macrophages

Publisher Summary The membrane molecules play an important role in all aspects of macrophage immunobiology. Some of the roles played by them are as receptors for growth and differentiation factors, as chemokines and lymphokines, as recognition and adhesion molecules for cellular and microbial ligands, and as regulators of cell signaling and gene expression. They determine and modulate homeostatic interactions with the host, contribute to innate and adaptive immunity, and mediate many of the pathological consequences of deficient or excessive activation. Some general aspects of macrophage heterogeneity are summarized and the differential expression of macrophage antigens is considered in this chapter as a function of tissue localization and cellular activity. Some of the differentiation antigens expressed by murine monocytes and macrophages are discussed—namely, EGF-TM7 antigens, IgSF antigens, and lectins. There are a number of molecules that function as scavenger receptors, several of which lack collagenous domains. Two such well-characterized antigens that play crucial roles in macrophage biology are scavenger receptor and MARCO.

MYELOID-SPECIFIC GENE EXPRESSION

The mononuclear phagocytes are recruited from bone marrow precursors to most tissues of the body, particularly during inflammation or immune stimulation. This combination of accessibility as stem cells and heterogenity of tissue locations makes the myeloid cell potentially important as a carrier of therapeutic agents. Understanding the regulation of transcription in myeloid cells is necessary for any future design of tissue‐specific gene targeting vectors, particularly if there are inherent size limitations. Identified members of the C/EBP, Runt/PEBP2/CBF, and Ets families of transcription factors are critical for myeloid‐specific gene expression and may have myeloid‐restricted expression or myeloid‐specific regulation in the hematopoietic system. AP‐1, Sp1, and Myb appear to be important for myeloid‐restricted expression in some cases. In addition, factors involved in the up‐regulation of the level of gene expression when macrophages are activated by agents such as interferon‐γ and bacterial products have been identified. Some of the sequences to which these transcription factors bind in myeloid‐restricted genes have been tested in cell lines and in transgenic mice and it is now possible to make an attempt to describe the characteristics of a myeloid‐specific promoter. J. Leukoc. Biol. 63: 153–168; 1998.

Class A scavenger receptors and the phagocytosis of apoptotic cells.

Apoptotic cells are rarely seen in situ because of rapid clearance by phagocytes. A number of receptors have been implicated in the recognition and ingestion of dying cells. Class A scavenger receptors (SRs) are multi-domained membrane glycoproteins that can endocytose modified lipoproteins and bind a wide range of ligands. There is growing evidence that they contribute to several biological processes. We present data that suggest class A SRs are involved in the phagocytosis of apoptotic cells.