Published Online
on July 5, 2005

A more recent version of this article appeared on July 12, 2005

This Article Full Text (PDF) All Versions of this Article: 112/2/241    most recent CIRCULATIONAHA.105.535625v1 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 Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hannawa, K. K. Articles by Upchurch, G. R. Search for Related Content PubMed PubMed Citation Articles by Hannawa, K. K. Articles by Upchurch, G. R., Jr Pubmed/NCBI databases Gene GEO Profiles HomoloGene Protein UniGene Substance via MeSH Medline Plus Health Information Aortic Aneurysm Related Collections Animal models of human disease CV surgery: aortic and vascular disease Other Vascular biology Related Article

Submitted on January 11, 2005
Revised on April 14, 2005
Accepted on April 18, 2005

L-Selectin-Mediated Neutrophil Recruitment in Experimental Rodent Aneurysm Formation

Kevin K. Hannawa BS, Jonathan L. Eliason MD, Derek T. Woodrum MD, Charles G. Pearce BA, Karen J. Roelofs DVM, Vladimir Grigoryants MD, Matthew J. Eagleton MD, Peter K. Henke MD, Thomas W. Wakefield MD, Daniel D. Myers DVM, MPH, James C. Stanley MD, and Gilbert R. Upchurch Jr MD^*

From the Jobst Vascular Research Laboratories, Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, Mich.

^* To whom correspondence should be addressed. E-mail: riversu{at}umich.edu.

Background--This investigation tested the hypothesis that L-selectin is important in experimental abdominal aortic aneurysm (AAA) formation in rodents.

Methods and Results--Rat abdominal aortas were perfused with saline (control) or porcine pancreatic elastase and studied on postperfusion days 1, 2, 4, 7, and 14 (n=5 per treatment group per day). Neutrophil (polymorphonucleur leukocyte, PMN) and macrophage counts per high-powered field (HPF) were performed on fixed sections. L-selectin expression and protein levels in aortic tissue were determined by polymerase chain reaction and Western blot, respectively. Elastase-perfused aortic diameters were significantly increased compared with control aortas at all time points except day 1 (P<0.05). PMN counts significantly increased in elastase-perfused aortas compared with control aortas at days 1, 2, and 4, reaching maximum levels at day 7 (40.8 versus 0.3 PMNs/HPF, P=0.001). L-selectin mRNA expression in elastase-perfused aortas was 18 (P=0.018), 17 (P<0.001), and 8 times (P=0.02) times greater than control aortas at days 1, 2, and 4, respectively. Western blot demonstrated a significant 69% increase in L-selectin protein at day 7 in elastase- as compared with saline-perfused aortas (P=0.005). Subsequent experiments involved similar studies on postperfusion days 4, 7, and 14 of aortas from C57BL/6 wild-type (WT) mice (n=21) and L-selectin-knockout (LKO) mice (n=19). LKO mice had significantly smaller aortic diameters at day 14 as compared with WT mice (88% versus 123%, P=0.02). PMN counts were significantly greater in elastase-perfused WT mouse aortas as compared with LKO mouse aortas at day 4 after perfusion (12.8 versus 4.8 PMNs/HPF, P=0.02). Macrophage counts were significantly greater at all time points after perfusion in elastase-perfused WT mouse aortas compared with elastase-perfused LKO mouse aortas, with a maximum difference at day 7 after perfusion (13.3 versus 0.5 macrophages/HPF, P<0.001).

Conclusion--L-selectin-mediated neutrophil recruitment may be a critical early step in AAA formation.

Key words: aneurysm • aorta • cell adhesion molecules • leukocytes

Related Article:

The Polymorphonuclear Leukocyte and the Abdominal Aortic Aneurysm: A Neglected Cell Type and a Neglected Disease

M. David Tilson, III
Circulation 2005 112: 154-156. [Extract] [Full Text]

This article has been cited by other articles:

				X. Houard, Z. Touat, V. Ollivier, L. Louedec, M. Philippe, U. Sebbag, O. Meilhac, P. Rossignol, and J.-B. Michel Mediators of neutrophil recruitment in human abdominal aortic aneurysms Cardiovasc Res, June 1, 2009; 82(3): 532 - 541. [Abstract] [Full Text] [PDF]

				X. Houard, V. Ollivier, L. Louedec, J.-B. Michel, and M. Back Differential inflammatory activity across human abdominal aortic aneurysms reveals neutrophil-derived leukotriene B4 as a major chemotactic factor released from the intraluminal thrombus FASEB J, May 1, 2009; 23(5): 1376 - 1383. [Abstract] [Full Text] [PDF]

				Z. Touat, V. Ollivier, J. Dai, M.-G. Huisse, A. Bezeaud, U. Sebbag, T. Palombi, P. Rossignol, O. Meilhac, M.-C. Guillin, et al. Renewal of Mural Thrombus Releases Plasma Markers and Is Involved in Aortic Abdominal Aneurysm Evolution Am. J. Pathol., March 1, 2006; 168(3): 1022 - 1030. [Abstract] [Full Text] [PDF]

				M. D. Tilson III The Polymorphonuclear Leukocyte and the Abdominal Aortic Aneurysm: A Neglected Cell Type and a Neglected Disease Circulation, July 12, 2005; 112(2): 154 - 156. [Full Text] [PDF]