[Frontiers in Bioscience 14, 929-943, January 1, 2009]

Ectoenzymes and innate immunity: the role of human CD157 in leukocyte trafficking

Ada Funaro1,2, Erika Ortolan1,2, Paola Bovino1, Nicola Lo Buono1, Giulia Nacci1, Rossella Parrotta1, Enza Ferrero1,2, Fabio Malavasi1,2

1 Department of Genetics, Biology and Biochemistry, and 2Research Center on Experimental Medicine (CeRMS), University of Torino Medical School, Via Santena 19, 10126 Torino, Italy

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. CD157 and the ADPRC gene family
3.1. Phylogenetic analysis
3.2. CD157 and CD38 gene structure and regulation
3.3. Gene modifications underlie differences in NADase/ADPRC protein topology
3.4. CD157 protein structure
3.5. CD157 tissue distribution
3.6. CD157 expression during inflammation
4. CD157 functions
4.1. Enzymatic functions
4.2. Immunoregulatory functions
5. Role of CD157 in leukocyte trafficking.
5.1. Role of CD157 in neutrophil polarization
5.2. Functional and molecular interactions between CD157 and the CD11b/CD18 complex
5.3. Receptorial activities of CD157 on vascular endothelial cells
5.4. Role of CD157 in neutrophil transendothelial migration
5.5. Role of CD157 in neutrophil adhesion and chemotaxis
5.6. The Paroxysmal Nocturnal Hemoglobinuria (PNH) disease model
6. Summary and perspectives
7. Acknowledgments
8. References

1. ABSTRACT

CD157 is a glycosylphosphatidylinositol-anchored molecule encoded by a member of the CD38/ADP-ribosyl cyclase gene family, involved in the metabolism of NAD. Expressed mainly by cells of the myeloid lineage and by vascular endothelial cells, CD157 has a dual nature behaving both as an ectoenzyme and as a receptor. Although it lacks a cytoplasmic domain, and cannot transduce signals on its own, the molecule compensates for this structural limit by interacting with conventional receptors. Recent experimental evidence suggests that CD157 orchestrates critical functions of human neutrophils. Indeed, CD157-mediated signals promote cell polarization, regulate chemotaxis induced through the high affinity fMLP receptor and control transendothelial migration.