Matrix metalloproteinase 9 production by monocytes is enhanced by TNF and participates in the pathology of human cutaneous Leishmaniasis.
BACKGROUND
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.
Serviço de Imunologia, Universidade Federal da Bahia, Salvador, Bahia, Brazil.
Taís M
TM
Campos
Serviço de Imunologia, Universidade Federal da Bahia, Salvador, Bahia, Brazil; Instituto Nacional de Ciências e Tecnologia - Doenças Tropicais, Salvador, Bahia, Brazil.
Sara T
ST
Passos
Department of Pathobiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Fernanda O
FO
Novais
Department of Pathobiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Daniel P
DP
Beiting
Serviço de Imunologia, Universidade Federal da Bahia, Salvador, Bahia, Brazil.
Rúbia S
RS
Costa
Serviço de Imunologia, Universidade Federal da Bahia, Salvador, Bahia, Brazil.
Adriano
A
Queiroz
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland, United States of America.
David
D
Mosser
Department of Pathobiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Phillip
P
Scott
Serviço de Imunologia, Universidade Federal da Bahia, Salvador, Bahia, Brazil; Instituto Nacional de Ciências e Tecnologia - Doenças Tropicais, Salvador, Bahia, Brazil.
Edgar M
EM
Carvalho
Serviço de Imunologia, Universidade Federal da Bahia, Salvador, Bahia, Brazil; Instituto Nacional de Ciências e Tecnologia - Doenças Tropicais, Salvador, Bahia, Brazil; Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador, Bahia, Brazil.
Lucas P
LP
Carvalho
D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D016773:Leishmaniasis, Cutaneous / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D007963:Leukocytes, Mononuclear / Q000201:enzymology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000378:metabolism; D009000:Monocytes / Q000201:enzymology*; D020411:Oligonucleotide Array Sequence Analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation
D061965:Matrix Metalloproteinase Inhibitors; C560822:TIMP1 protein, human; C439524:TNF protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; D020780:Matrix Metalloproteinase 9