Immunohistochemical study of type I collagen turn-over and of matrix metalloproteinases in chromoblastomycosis before and after treatment by terbinafine.
The distribution of type I collagen, the major component of human dermis, was characterized by immunohistochemistry in skin lesions of chromoblastomycosis, a chronic cutaneous mycosis, before and after a specific antifungal treatment with terbinafine to study the changes induced in the lesions by the treatment. Newly synthesized type I collagen was studied with an antibody directed against the aminoterminal propeptide of the molecule (PINP), whereas mature, cross-linked type I collagen was detected with an antibody against the carboxyterminal telopeptide of type I collagen (ICTP). The isopeptide N epsilon gamma-glutamyl lysine (N epsilon gamma GL), synthesized by transglutaminase and able to cross-link several components of the extracellular matrix, has also been investigated with two monoclonal antibodies to determine if it is involved in the stabilisation of the fibrotic cutaneous lesions. The degradative process involved in the remodelling has also been assessed by immunohistochemistry with anti-metalloproteinase (MMP-1 and MMP-9) and anti-tissue inhibitor (TIMP-1) antibodies. All tissue macrophages stained for CD68 and MMP-9, but not for MMP-1, while the polymorphonuclear neutrophils had an elastase and a weak MMP-9 phenotype. The fibroblasts of fibrotic areas stained constantly for N epsilon gamma GL and PINP. The immunostaining of extracellular matrix for ICTP and N epsilon gamma GL, and the number of PINP-positive fibroblasts, decreased significantly after one year of antifungal treatment. Terbinafine treatment decreases the synthesis of type I collagen and leads to a partial reversal of the cutaneous fibrotic lesions, independently of the cure of the fungal infection.
Esterre
P
P
Parasitology Unit, Institut Pasteur de Madagascar, Antananarivo, Madagascar.
Risteli
L
L
Ricard-Blum
S
S
D000935:Antifungal Agents / Q000627:therapeutic use*; D002862:Chromoblastomycosis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D003094:Collagen / Q000378:metabolism*; D017364:Collagenases / Q000378:metabolism*; D005109:Extracellular Matrix / Q000737:chemistry; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D020781:Matrix Metalloproteinase 1; D020780:Matrix Metalloproteinase 9; D008875:Middle Aged; D009281:Naphthalenes / Q000627:therapeutic use*; D009504:Neutrophils / Q000201:enzymology; D010196:Pancreatic Elastase / Q000378:metabolism; D000077291:Terbinafine; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
D000935:Antifungal Agents; D009281:Naphthalenes; D019715:Tissue Inhibitor of Metalloproteinase-1; D003094:Collagen; D010196:Pancreatic Elastase; D017364:Collagenases; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1; D000077291:Terbinafine