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

Hannawa, Kevin K.; Eliason, Jonathan L.; Woodrum, Derek T.; Pearce, Charles G.; Roelofs, Karen J.; Grigoryants, Vladimir; Eagleton, Matthew J.; Henke, Peter K.; Wakefield, Thomas W.; Myers, Daniel D.; Stanley, James C.; Upchurch, Gilbert R.

doi:10.1161/circulationaha.105.535625

Cited by 64 publications

(67 citation statements)

References 33 publications

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“…Rat models, however, have been widely employed for studying ligament and tendon healing [57][58][59] and inflammation. 44,57,60 In addition, PrT injections are typically performed on chronically painful and loose joints. Chronic overuse and long-term injury animal models are not easily developed or typically used.…”

Section: Discussionmentioning

confidence: 99%

Early inflammatory response of knee ligaments to prolotherapy in a rat model

Jensen

Rabago

Best

et al. 2008

Journal Orthopaedic Research

122

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Prolotherapy is an alternative injection-based therapy for chronic musculoskeletal pain. Three different proliferants, D-glucose (dextrose), phenol-glucose-glycerine (P2G), and sodium morrhuate, used in prolotherapy are hypothesized to strengthen and reorganize chronically injured soft tissue and decrease pain through modulation of the inflammatory process. Our hypothesis is that commonly used prolotherapy solutions will induce inflammation (leukocyte and macrophage infiltration) in medial collateral ligaments (MCLs) compared to needlestick, saline injection, and no-injection controls. MCLs of 84 Sprague-Dawley rats were injected one time at both the tibial and femoral insertions. Immunohistochemistry (IHC) was used to determine the inflammatory response at three locations (tibial and femoral insertions and midsubstance) 6, 24, and 72 h after dextrose injection compared to saline-and no-injection controls and collagenase (positive control) (n ¼ 4). qPCR was used to analyze gene expression 24 h postinjection (n ¼ 4). Sodium morrhuate, P2G, and needlestick control were also investigated after 24 h (n ¼ 4). In general, inflammation (CD43þ, ED1þ, and ED2þ cells) increased after prolotherapy injection compared to no-injection control but did not increase consistently compared to saline and needlestick control injections. This response varied by both location and proliferant. Inflammation was observed at 6 and 24 h postinjection but was resolved by 72 h compared to no-injection controls (p < 0.05). CD43þ leukocytes and ED2þ macrophages increased compared to needlestick and saline-injection control, respectively, 24 h postinjection (p < 0.05). Prolotherapy injections created an inflammatory response, but this response was variable and overall, not uniformly different from that caused by saline injections or needlestick procedures. ß

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Section: Discussionmentioning

confidence: 99%

Early inflammatory response of knee ligaments to prolotherapy in a rat model

Jensen

Rabago

Best

et al. 2008

Journal Orthopaedic Research

122

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“…Immunoreactive neutrophils are also evident within the adventitia and mural thrombus of AAAs, suggesting that release of neutrophil serine proteases might play an important but poorly understood role in aneurysmal degeneration (16,17). This notion is supported by more recent studies indicating that neutrophil depletion can suppress the development of experimental AAAs (18,19).…”

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confidence: 84%

Critical role of dipeptidyl peptidase I in neutrophil recruitment during the development of experimental abdominal aortic aneurysms

Pagano

Bartoli

Ennis

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

120

121

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Dipeptidyl peptidase I (DPPI) is a lysosomal cysteine protease critical for the activation of granule-associated serine proteases, including neutrophil elastase, cathepsin G, and proteinase 3. DPPI and granule-associated serine proteases have been shown to play a key role in regulating neutrophil recruitment at sites of inflammation. It has recently been suggested that neutrophils and neutrophil-associated proteases may also be important in the development and progression of abdominal aortic aneurysms (AAAs), a common vascular disease associated with chronic inflammation and destructive remodeling of aortic wall connective tissue. Here we show that mice with a loss-of-function mutation in DPPI are resistant to the development of elastase-induced experimental AAAs. This is in part because of diminished recruitment of neutrophils to the elastase-injured aortic wall and impaired local production of CXC-chemokine ligand (CXCL) 2. Furthermore, adoptive transfer of wild-type neutrophils is sufficient to restore susceptibility to AAAs in DPPI-deficient mice, as well as aortic wall expression of CXCL2. In addition, in vivo blockade of CXCL2 by using neutralizing antibodies directed against its cognate receptor leads to a significant reduction in aortic dilatation. These findings suggest that DPPI and/or granule-associated serine proteases are necessary for neutrophil recruitment into the diseased aorta and that these proteases act to amplify vascular wall inflammation that leads to AAAs. cardiovascular ͉ inflammation ͉ innate immunity ͉ proteases

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“…Established techniques using TRIzol reagent (Invitrogen, Carlsbad, CA) were used to extract mRNA for real-time RT-PCR (10,17). In brief, explanted aortic tissue was added to 1.5 ml TRIzol reagent, and the tissue was homogenized.…”

Section: Experimental Protocol Male and Female Wild-type (Wt) And Pai-1mentioning

confidence: 99%

“…For Western blot analysis, the tissues were lysed by sonication and overnight incubation in ice-cold RIPA buffer (Sigma) containing protease and phosphatase inhibitors (Roche, Basel, Switzerland) (9,10,17). Protein concentration in the lysate was determined with the BCA protein assay kit (Pierce, Rockford, IL).…”

Section: Experimental Protocol Male and Female Wild-type (Wt) And Pai-1mentioning

confidence: 99%

Increased PAI-1 in females compared with males is protective for abdominal aortic aneurysm formation in a rodent model

DiMusto

Ghosh

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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The serine proteases, along with their inhibitor plasmin activator inhibitor-1 (PAI-1), have been shown to play a role in abdominal aortic aneurysm (AAA) formation. The aim of this study is to determine if PAI-1 may be a protective factor for AAA formation and partially responsible for the gender difference observed in AAAs. Male and female wild-type (WT) C57BL/6 and PAI-1−/−mice 8–12 wk of age underwent aortic perfusion with porcine pancreatic elastase. Animals were harvested 14 days following perfusion and analyzed for phenotype, PAI-1 protein levels, and matrix metalloproteinase (MMP)-9 and -2 activity. WT males had an average increase in aortic diameter of 80%, whereas females only increased 32% ( P < 0.001). PAI-1−/−males increased 204% and females 161%, significantly more than their WT counterparts ( P < 0.001). Western blot revealed 61% higher PAI-1 protein levels in the WT females compared with the WT males ( P = 0.01). Zymography revealed higher levels of pro-MMP-2 and active MMP-2 in the PAI-1−/−males and females compared with their WT counterparts. PAI-1−/−females had significantly higher serum plasmin levels compared with WT females ( P = 0.003). In conclusion, WT female mice are protected from aneurysm formation and have higher levels of PAI-1 compared with males during experimental aneurysm formation. Additionally, both male and female PAI-1−/−animals develop significantly larger aneurysms than WT animals, correlating with higher pro- and active MMP-2 levels. These findings suggest that PAI-1 is protective for aneurysm formation in the elastase model of AAA and plays a role in the gender differences seen in AAA formation.

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

Cited by 64 publications

References 33 publications

Early inflammatory response of knee ligaments to prolotherapy in a rat model

Early inflammatory response of knee ligaments to prolotherapy in a rat model

Critical role of dipeptidyl peptidase I in neutrophil recruitment during the development of experimental abdominal aortic aneurysms

Increased PAI-1 in females compared with males is protective for abdominal aortic aneurysm formation in a rodent model

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