BBA - Molecular and Cell Biology of Lipids
Lysophospholipids
Edited by G. Tigyi
Volume 1781, Issue 9, Pages 423-600 (September 2008)

Oftentimes we refer to lysophospholipids as nature's simplest phospholipids endowed with the most complex biological effects. The field of lysophospholipid research has now grown beyond its childhood and is gaining recognition in disciplines that range from immunology to neuroscience. With the identification of sphingosine-1-phosphate (S1P) receptors as targets of the immunomodulator drug FTY-720, now in phase III clinical trials, this field has begun to contribute novel therapies to human disease. Yet we all know that our present understanding of the lysophospholipids, their mechanism of action, and their physiological and pathophysiological roles is still highly incomplete.

Since 2001, the FASEB Summer Conference series has provided a forum for investigators in this field to meet biannually to discuss and assess progress in our understanding of lysophospholipid biology and pathobiology. During our meeting in Tucson in 2007, I solicited contributions from leading investigators in the field for this special issue of Biophysica et Biochimica Acta: Molecular and Cell Biology of Lipids. I did this with the intent of providing investigators in the field with a comprehensive and up-to-date progress report on the main issues facing us and also to provide readers from other fields with a perspective on the main issues and emerging topics for future investigations in the rapidly developing area of lipid research.

Undoubtedly, we have come a long way since lysophosphatidic acid (LPA) was called a “lytic precipitating artifact” and sphingosine-1-phosphate was considered just an intermediate product of sphingolipid metabolism. The perception of lysophospholipid receptors has taken a 180-degree turn from the skepticism of the early 1990s and has changed to an amazing complexity with the identification of six S1P receptors and nine LPA receptors. Identification of sphingosine kinases and lysophospholipase D/autotaxin has reshaped the thinking about the role of lysophospholipid products in physiology and pathophysiology. The ubiquitous presence of lysophospholipid mediators and their molecular targets presents a new dilemma: how can we conceptualize the specificity and diversity of lysophospholipid action? This issue is likely to take center stage in future research as we gain insight into the highly localized biological effects of lysophospholipids in tissues with distinct cell types. Once these unique events and sites of action have been identified, the field will be better positioned to explore them as targets of drug discovery. With abundant expression of lysophospholipid targets in the nervous system, in the immune system, in the cardiovascular system, and in every major and minor organ, the opportunities are endless and inspiring. Knowledge of the chemical biology of lysophospholipids is developing very rapidly, and drugable non-lipid agonists and antagonists of lysophospholipid targets are being developed through rational drug design and being identified by high-throughput screens of huge compound libraries.

I thank all the contributors for their excellent papers and the reviewers for their rapid turnaround of the reviews. I thank Jessica Abercombie for expert handling of the submissions. I compliment the vision of BBA Editor-in-Chief Dennis Vance and Editors Fritz Spener and Bill Dowhan of BBA: Molecular and Cellular Biology of Lipids for recognizing the timeliness of publishing this collection of reviews. I hope that this compilation of articles will further the tradition of discussion and assessment that we have developed in the lysophospholipid field, and that BBA will continue to publish special issues every four years dedicated to progress in lysophospholipid research.