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Matrix metalloproteinase 9 production by monocytes is enhanced by TNF and participates in the pathology of human cutaneous Leishmaniasis.

Campos TM, Passos ST, Novais FO, Beiting DP, Costa RS, Queiroz A, Mosser D, Scott P, Carvalho EM, Carvalho LP - PLoS Negl Trop Dis (2014)

Bottom Line: Culture was performed during 72 hours, stimulating the cells with SLA, levels of MMP-9 and TIMP-1 in the supernatants were determined by ELISA.We observed that cells from CL lesions secrete high amounts of MMP-9 when compared to healthy subjects.We also observed that TNF produced in high level during CL contributes to MMP-9 production.

View Article: PubMed Central - PubMed

Affiliation: Serviço de Imunologia, Universidade Federal da Bahia, Salvador, Bahia, Brazil.

ABSTRACT

Introduction: Cutaneous leishmaniasis (CL) due to L.braziliensis infection is characterized by a strong inflammatory response with high levels of TNF and ulcer development. Less attention has been given to the role of mononuclear phagocytes to this process. Monocytes constitute a heterogeneous population subdivided into classical, intermediate and non-classical, and are known to migrate to inflammatory sites and secrete inflammatory mediators. TNF participates in the induction of matrix metalloproteinases (MMPs). MMP-9 is an enzyme that degrades basal membrane and its activity is controlled by the tissue inhibitor of metalloproteinase.

Methods: Mononuclear cells were obtained from ex-vivo labeling sub-populations of monocytes and MMP-9, and the frequency was determined by flow cytometry. Culture was performed during 72 hours, stimulating the cells with SLA, levels of MMP-9 and TIMP-1 in the supernatants were determined by ELISA.

Results: We observed that cells from CL lesions secrete high amounts of MMP-9 when compared to healthy subjects. Although MMP-9 was produced by monocytes, non-classical ones were the main source of this enzyme. We also observed that TNF produced in high level during CL contributes to MMP-9 production.

Conclusions: These observations emphasize the role of monocytes, TNF and MMP-9 in the pathogenesis of L. braziliensis infection.

No MeSH data available.


Related in: MedlinePlus

Monocytes are important source of MMP-9 in CL.PBMC were obtained from healthy subjects (HS) and CL patients and intracellular labeling to MMP-9 was performed ex-vivo. The frequency of CD4+, CD8+ and CD14+ cells positive to MMP-9 was determined by flow cytometry. The gate strategy was done using all minus one staining. A, representative plots from HS (n = 5). B, representative plots from CL patients (n = 5).
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pntd-0003282-g003: Monocytes are important source of MMP-9 in CL.PBMC were obtained from healthy subjects (HS) and CL patients and intracellular labeling to MMP-9 was performed ex-vivo. The frequency of CD4+, CD8+ and CD14+ cells positive to MMP-9 was determined by flow cytometry. The gate strategy was done using all minus one staining. A, representative plots from HS (n = 5). B, representative plots from CL patients (n = 5).

Mentions: It has been documented that leucocytes are the main source of MMP-9 [29], [30] and our results show that PBMCs from CL patients secrete high levels of MMP-9 in response to SLA. To further characterize the source of MMP-9 in CL patients, using flow cytometry we determined the ex-vivo production of MMP-9 by CD4+ and CD8+ T cells, and monocytes based on CD14 expression. Our results show that monocytes are the main source of this enzyme in HS and patients with CL (Figure 3A and B).


Matrix metalloproteinase 9 production by monocytes is enhanced by TNF and participates in the pathology of human cutaneous Leishmaniasis.

Campos TM, Passos ST, Novais FO, Beiting DP, Costa RS, Queiroz A, Mosser D, Scott P, Carvalho EM, Carvalho LP - PLoS Negl Trop Dis (2014)

Monocytes are important source of MMP-9 in CL.PBMC were obtained from healthy subjects (HS) and CL patients and intracellular labeling to MMP-9 was performed ex-vivo. The frequency of CD4+, CD8+ and CD14+ cells positive to MMP-9 was determined by flow cytometry. The gate strategy was done using all minus one staining. A, representative plots from HS (n = 5). B, representative plots from CL patients (n = 5).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230914&req=5

pntd-0003282-g003: Monocytes are important source of MMP-9 in CL.PBMC were obtained from healthy subjects (HS) and CL patients and intracellular labeling to MMP-9 was performed ex-vivo. The frequency of CD4+, CD8+ and CD14+ cells positive to MMP-9 was determined by flow cytometry. The gate strategy was done using all minus one staining. A, representative plots from HS (n = 5). B, representative plots from CL patients (n = 5).
Mentions: It has been documented that leucocytes are the main source of MMP-9 [29], [30] and our results show that PBMCs from CL patients secrete high levels of MMP-9 in response to SLA. To further characterize the source of MMP-9 in CL patients, using flow cytometry we determined the ex-vivo production of MMP-9 by CD4+ and CD8+ T cells, and monocytes based on CD14 expression. Our results show that monocytes are the main source of this enzyme in HS and patients with CL (Figure 3A and B).

Bottom Line: Culture was performed during 72 hours, stimulating the cells with SLA, levels of MMP-9 and TIMP-1 in the supernatants were determined by ELISA.We observed that cells from CL lesions secrete high amounts of MMP-9 when compared to healthy subjects.We also observed that TNF produced in high level during CL contributes to MMP-9 production.

View Article: PubMed Central - PubMed

Affiliation: Serviço de Imunologia, Universidade Federal da Bahia, Salvador, Bahia, Brazil.

ABSTRACT

Introduction: Cutaneous leishmaniasis (CL) due to L.braziliensis infection is characterized by a strong inflammatory response with high levels of TNF and ulcer development. Less attention has been given to the role of mononuclear phagocytes to this process. Monocytes constitute a heterogeneous population subdivided into classical, intermediate and non-classical, and are known to migrate to inflammatory sites and secrete inflammatory mediators. TNF participates in the induction of matrix metalloproteinases (MMPs). MMP-9 is an enzyme that degrades basal membrane and its activity is controlled by the tissue inhibitor of metalloproteinase.

Methods: Mononuclear cells were obtained from ex-vivo labeling sub-populations of monocytes and MMP-9, and the frequency was determined by flow cytometry. Culture was performed during 72 hours, stimulating the cells with SLA, levels of MMP-9 and TIMP-1 in the supernatants were determined by ELISA.

Results: We observed that cells from CL lesions secrete high amounts of MMP-9 when compared to healthy subjects. Although MMP-9 was produced by monocytes, non-classical ones were the main source of this enzyme. We also observed that TNF produced in high level during CL contributes to MMP-9 production.

Conclusions: These observations emphasize the role of monocytes, TNF and MMP-9 in the pathogenesis of L. braziliensis infection.

No MeSH data available.


Related in: MedlinePlus