Matrix Metalloproteinase-9 Deficiency Impairs Host Defense against Abdominal Sepsis

Renckens, Rosemarijn; Roelofs, Joris J. T. H.; Florquin, Sandrine; Vos, Alex F. de; Lijnen, H. Roger; Veer, Cornelis van’t; Poll, Tom van der

doi:10.4049/jimmunol.176.6.3735

Cited by 109 publications

(92 citation statements)

References 37 publications

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“…We have found a significant increase in myeloperoxidase activity, a surrogate marker of neutrophil infiltration, in BAL fluid from Mmp9 Ϫ/Ϫ mice after injurious ventilation. Renckens and coworkers (39) have found a similar increase in myeloperoxidase activity in the lungs of Mmp9 Ϫ/Ϫ animals after experimental induction of peritonitis.…”

Section: Discussionmentioning

confidence: 64%

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Lack of matrix metalloproteinase-9 worsens ventilator-induced lung injury

Albaiceta¹,

Gutiérrez‐Fernández²,

Parra³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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Section: Discussionmentioning

confidence: 64%

“…Currently, MMPs are viewed as modulators of cell-cell and cell-matrix interactions (37). Among them, MMP-9 (gelatinase B) has gained some attention in different models of lung injury (39,42) including VILI (14,25). The levels of MMP-9 have also been found to be raised in patients with acute lung injury (13,40,50).…”

mentioning

confidence: 98%

Lack of matrix metalloproteinase-9 worsens ventilator-induced lung injury

Albaiceta¹,

Gutiérrez‐Fernández²,

Parra³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…decreased levels of RANTES) cannot be excluded. The metalloproteinases (MMP) that are thought to contribute to leukocyte recruitment [50,51] most likely do not play a major role in the model employed, as we detected neither lack of induction of either MMP9 or MMP2 in the peritoneal cavity during peritonitis, nor any difference in trans-endothelial migration of MMP9-/-lymphocytes compared to controls (data not shown). This is in agreement with the observation of Betsuyaku et.…”

Section: Discussionmentioning

confidence: 84%

Unique and redundant roles of α4 and β2 integrins in kinetics of recruitment of lymphoid vs myeloid cell subsets to the inflamed peritoneum revealed by studies of genetically deficient mice

Ulyanova

Priestley

Banerjee

et al. 2007

Experimental Hematology

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OBJECTIVE-Leukocyte recruitment to inflammatory sites is a prominent feature of acute and chronic inflammation. Instrumental in this process is the coordinated upregulation of leukocyte integrins (among which α4β1 and β2 integrins are major players) and their cognate receptors in inflamed tissues. To avoid the ambiguity of previous short-term antibody-based studies and to allow for long-term observation, we used genetically deficient mice to compare roles of α4 and β2 integrins in leukocyte trafficking.METHODS-Aseptic peritonitis was induced in α4 or β2 integrin-deficient (conditional and conventional knockouts, respectively) and control mice, and recruitment of major leukocyte subsets to the inflamed peritoneum was followed for up to 4 days. RESULTS-Despite normal chemokine levels in the peritoneum and adequate numbers, optimal recruitment of myeloid cells was impaired in both α4-and β2-deficient mice. Furthermore, clearance of recruited neutrophils and macrophages was delayed in these mice. Lymphocyte migration to the peritoneum in the absence of α4 integrins was drastically decreased, both at steady state and during inflammation, a finding consistent with impaired lymphocyte in vitro adhesion and signaling. By contrast, in the absence of β2 integrins, defects in lymphocyte recruitment were only evident when peritonitis was established.CONCLUSIONS-Our data with concurrent use of genetic models of integrin deficiency reveal non-redundant functions of α4 integrins in lymphocyte migration to the peritoneum and further refine specific roles of α4 and β2 integrins concerning trafficking and clearance of other leukocyte subsets at homeostasis and during inflammation.

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“…Phagocytosis of P. aeruginosa by neutrophils was determined as previously described (28,29) with minor modifications. P. aeruginosa was heat killed by incubation at 65°C for 1 h and labeled with 0.2 mg/ml FITC (Sigma-Aldrich) in 0.1 M NaHCO 3 (pH 9.0) for 1 h at 37°C.…”

Section: Phagocytosis Assaymentioning

confidence: 99%

Platelet-Activating Factor Receptor Contributes to Host Defense against Pseudomonas aeruginosa Pneumonia but Is Not Essential for the Accompanying Inflammatory and Procoagulant Response

Zoelen

Florquin²,

Meijers

et al. 2008

The Journal of Immunology

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Pseudomonas aeruginosa is a major cause of nosocomial pneumonia, which is associated with high morbidity and mortality. Because of its ubiquitous nature and its ability to develop resistance to antibiotics, it is a problematic pathogen from a treatment perspective. Platelet-activating factor receptor (PAFR) is involved in phagocytosis of several pathogens. To determine the role of PAFR in the innate immune response to P. aeruginosa pneumonia, pafr gene-deficient (PAFR−/−) mice and normal wild-type (Wt) mice were intranasally inoculated with P. aeruginosa. PAFR deficiency impaired host defense as reflected by increased bacterial outgrowth and dissemination in mice with a targeted deletion of the PAFR gene. PAFR−/− neutrophils showed a diminished phagocytosing capacity of P. aeruginosa in vitro. Relative to Wt mice, PAFR−/− mice demonstrated increased lung inflammation and injury as reflected by histopathology, relative lung weights and total protein concentrations in bronchoalveolar lavage fluid, which was accompanied by higher levels of proinflammatory cytokines in lung homogenates and plasma. In addition, PAFR deficiency was associated with exaggerated local and systemic activation of coagulation as determined by fibrin staining of lung tissue and pulmonary and plasma concentrations of thrombin-antithrombin complexes and D-dimer. These data suggest that PAFR is an essential component of an effective host response to P. aeruginosa pneumonia, at least partly via its contribution to the phagocytic properties of professional granulocytes. Additionally, our results indicate that PAFR signaling is not essential for the induction of a local and systemic inflammatory and procoagulant response to Pseudomonas pneumonia.

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Matrix Metalloproteinase-9 Deficiency Impairs Host Defense against Abdominal Sepsis

Cited by 109 publications

References 37 publications

Lack of matrix metalloproteinase-9 worsens ventilator-induced lung injury

Lack of matrix metalloproteinase-9 worsens ventilator-induced lung injury

Unique and redundant roles of α4 and β2 integrins in kinetics of recruitment of lymphoid vs myeloid cell subsets to the inflamed peritoneum revealed by studies of genetically deficient mice

Platelet-Activating Factor Receptor Contributes to Host Defense against Pseudomonas aeruginosa Pneumonia but Is Not Essential for the Accompanying Inflammatory and Procoagulant Response

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