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Blood, 1 August 2007, Vol. 110, No. 3, pp. 794-795. 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 Michelson, A. D. Articles by Newburger, P. E. Search for Related Content PubMed Articles by Michelson, A. D. Articles by Newburger, P. E. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES Comment on Haselmayer et al, page 1029 Platelets and leukocytes: aggregate knowledge Alan D. Michelson, and Peter E. Newburger UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL In this issue of Blood, Haselmayer and colleagues demonstrate that platelets express the ligand for the triggering receptor expressed on myeloid cells 1 (TREM-1), and show that its interaction with neutrophil TREM-1 amplifies neutrophil activation. Patelets adhere to neutrophils and monocytes via a number of receptor/counterreceptor pairs (see figure).1 Activated platelets degranulate, thereby expressing platelet surface P-selectin. The initial adhesion of platelets to neutrophils and monocytes occurs via platelet surface P-selectin binding to its constitutively expressed leukocyte counterreceptor, P-selectin glycoprotein ligand 1 (PSGL-1). Stabilization of leukocyte-platelet aggregates occurs via the binding of leukocyte surface Mac-1 (also known as integrin Mß2 and CD11b/CD18) to platelet surface glycoprotein Ib (GPIb). In addition, leukocyte surface Mac-1 binds to the platelet surface integrin IIbß3 (with fibrinogen as a bridging molecule) and/or to platelet surface junctional adhesion molecule 3 (JAM-3). View larger version (72K): [in this window] [in a new window]   Receptor/counterreceptor pairs involved in platelet-neutrophil interactions. Professional illustration by Marie Dauenheimer.   Haselmayer and colleagues have now identified an additional receptor/counterreceptor pair involved in this process: neutrophil surface TREM-1 and platelet surface TREM-1 ligand. The interaction between TREM-1 and TREM-1 ligand is not required for neutrophil-platelet aggregate formation, but results in enhancement of neutrophil activation—as determined by respiratory burst activity and release of interleukin 8. TREM-1 is a member of the immunoglobulin superfamily and plays an important role in the innate immune response related to sepsis.2 However, the identity and location of the natural TREM-1 ligands were unknown. Haselmayer and colleagues have now discovered that TREM-1 ligand is expressed on human platelets. The platelet surface expression of TREM-1 ligand is not up-regulated by platelet activation, and the binding of TREM-1 to TREM-1 ligand on platelets does not result in platelet activation. These findings open up a number of new avenues for further investigation. First, the molecular identity of the TREM-1 ligand on platelets remains to be determined. Second, although Haselmayer and colleagues focus on neutrophil activation, TREM-1 is also expressed on monocytes.2 Therefore, the functional consequences of monocyte surface TREM-1 binding to platelet surface TREM-1 ligand should also be investigated. Third, given the role of the TREM-1/TREM-1 ligand interaction in sepsis,2 Haselmayer and colleagues raise the possibility of targeted therapy of this receptor/counterreceptor pair in the treatment of sepsis. Fourth, although not mentioned by Haselmayer et al, the study of the TREM-1/TREM-1 ligand interaction may also be fruitful in other inflammatory diseases in which monocyte-platelet and neutrophil-platelet aggregates play an important role. For example, circulating leukocyte-platelet aggregates, especially monocyte-platelet aggregates, promote the formation of atherosclerotic lesions,3 are increased in acute coronary syndromes, stroke, and peripheral vascular disease,4 and are an early marker of acute myocardial infarction.5 Increased circulating monocyte-platelet and neutrophil-platelet aggregates have also been reported in numerous other conditions, including diabetes mellitus, cystic fibrosis, asthma, pre-eclampsia, placental insufficiency, migraine, nephrotic syndrome, hemodialysis, sickle cell disease, systemic inflammatory response syndrome, septic multiple organ dysfunction syndrome, antiphospholipid syndrome, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, myeloproliferative disorders, Kawasaki disease, and Alzheimer disease.4 Future studies on TREM-1/TREM-1 ligand interactions will no doubt add to platelet and leukocyte aggregate knowledge. Footnotes Conflict-of-interest disclosure: The authors declare no competing financial interests. REFERENCES McEver RP. P-Selectin/PSGL-1 and other interactions between platelets, leukocytes, and endothelium. In Michelson AD (Ed.). Platelets 2nd ed. San Diego Elsevier/Academic Press 2007: pp. 231–249. Klesney-Tait J, Turnbull IR, Colonna M. The TREM receptor family and signal integration. Nat Immunol 2006; 7:1266–1273.[CrossRef][Medline] [Order article via Infotrieve] Huo Y, Schober A, Forlow SB, et al. Circulating activated platelets exacerbate atherosclerosis in mice deficient in apolipoprotein E. Nat Med 2003; 9:61–67.[CrossRef] Michelson AD, Linden MD, Barnard MR, Furman MI, Frelinger AL III. Flow cytometry. In Michelson AD (Ed.). Platelets 2nd ed. San Diego Elsevier/Academic Press 2007: pp. 545–564. Furman MI, Barnard MR, Krueger LA, et al. Circulating monocyte-platelet aggregates are an early marker of acute myocardial infarction. J Am Coll Cardiol 2001; 38:1002–1006.[Abstract/Free Full Text] CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: TREM-1 ligand expression on platelets enhances neutrophil activation Philipp Haselmayer, Ludger Grosse-Hovest, Philipp von Landenberg, Hansjörg Schild, and Markus P. Radsak Blood 2007 110: 1029-1035. [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 Michelson, A. D. Articles by Newburger, P. E. Search for Related Content PubMed Articles by Michelson, A. D. Articles by Newburger, P. E. 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