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Blood, 1 February 2008, Vol. 111, No. 3, pp. 979. This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Abrams, C. S. Search for Related Content PubMed Articles by Abrams, C. S. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  INSIDE BLOOD The yin-yang of platelet granules Charles S. Abrams UNIVERSITY OF PENNSYLVANIA SCHOOL OF MEDICINE Comment on Italiano et al, page 1227 Although platelets are often viewed as cells merely designed to plug up holes in the blood vessel wall, they do have the capacity to modify the vasculature in other ways. For example, a frequently overlooked function of platelets is to secrete a variety of substances that stimulate or inhibit blood and vascular cells. In turn, this process can modify the developing thrombus, contribute to cell-adhesive events, and regulate the growth of the vasculature. Platelets contain a wide variety of peptides and proteins, primarily in granules, that can modify the growth of cells in the vessel wall. The first of these compounds to be described was platelet-derived growth factor (PDGF). Platelets are the major storage cells for PDGF, and their secretion of this compound plays an important role in the proliferation of smooth muscle cells within the blood vessel wall. Consequently, platelet-secreted PDGF plays a critical role in angiogenesis. Other granule–contained modifiers of angiogenesis include vascular endothelial growth factor (VEGF), endostatin, thrombospondin, and basic fibroblast growth factor (FGF). View larger version (37K): [in this window] [in a new window]   Not all alpha granules are equal. Platelets contain alpha granules and dense granules. Italiano and colleagues show that some alpha granules contain antiangiogenesis factors, and other granules contain proangiogenesis factors. Stimulation of the PAR1 receptor causes the release of angiogenesis stimulants, while stimulation of the PAR4 receptor causes release of angiogenesis inhibitors.   Curiously, platelets contain substances that promote angiogenesis and other substances that inhibit local angiogenesis. Releasing both types of substances would seem to be counterproductive. Italiano and colleagues postulated that under certain circumstances, platelets might exclusively secrete specific granules that promote proangiogenesis, while in response to other types of stimulation, platelets might selectively secrete granules that promote antiangiogenesis. In order for this to be true, they further hypothesized that platelets could not contain both proangiogenesis and antiangiogenesis compounds within the same granule. In an illuminating series of experiments using double immunofluorescence or electron microscopy, the Italiano group convincingly proved both of their hypotheses. They showed that platelets contain particular granules loaded with angiogenesis stimulators and other granules loaded with angiogenesis inhibitors. Furthermore, they found that stimulation of one type of thrombin receptor (PAR4) stimulates the release of antiangiogenesis granules, whereas stimulation of the other type of thrombin receptor (PAR1) stimulates secretion of proangiogenesis granules. Their findings are surprising and raise a number of issues. How do platelets load and separate seemingly similar granules that contain physiologically competing compounds? Do platelets have discrete signaling pathways that release specific granules, or is it the strength and/or speed of the signal that causes the secretion of one exclusive class of granules? Are there markers on the surfaces of the granules that identify different classes of granules? Can therapeutics be designed to impair or enhance the release of an individual class of platelet granules? This article allows us a peek into the contents of the platelets' baggage, yet reminds us how much deeper we need to look.    Footnotes   DOI: 10.1182/blood-2007-11-122515 Footnotes Conflict-of-interest disclosure: The author declares no competing financial interests. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Angiogenesis is regulated by a novel mechanism: pro- and antiangiogenic proteins are organized into separate platelet granules and differentially released Joseph E. Italiano, Jr, Jennifer L. Richardson, Sunita Patel-Hett, Elisabeth Battinelli, Alexander Zaslavsky, Sarah Short, Sandra Ryeom, Judah Folkman, and Giannoula L. Klement Blood 2008 111: 1227-1233. [Abstract] [Full Text] [PDF] This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Abrams, C. S. Search for Related Content PubMed Articles by Abrams, C. S. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?

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