Expression of membrane type-4 matrix metalloproteinase (metalloproteinase-17) by human eosinophils.
Circulating eosinophils need proteinases to mediate a spatially limited and orientated digestion of the extracellular matrix and to migrate into tissue. Moreover, proteinases are likely involved in tissue remodeling, a crucial feature of chronic diseases including asthma. Eosinophils express matrix metalloproteinase (MMP)-9, which is increased upon stimulation with TNF-alpha. Other MMPs, the membrane type (MT)-MMPs, likely play a major role in cell invasion and tissue remodeling. MT4-MMP was identified in peripheral blood leukocyte preparations, but it is not known whether eosinophils express MT4-MMP. We investigated the expression of MT4-MMP and its modulation by TNF-alpha in purified human blood eosinophils. The constitutive expression of MT4-MMP mRNA was detected by RT-PCR in unstimulated eosinophils, lymphocytes, and monocytes, but not neutrophils. Stimulation of eosinophils with TNF-alpha increased MT4-MMP mRNA expression. This effect appeared at 4h and reached a maximum at 8h of incubation. MT4-MMP protein was detected in freshly isolated blood eosinophils by Western blotting and immunocytochemistry. TNF-alpha increased expression of the MT4-MMP protein. MT4-MMP protein was also detected in nasal polyp eosinophils by immunohistochemistry. In conclusion, eosinophils constitutively express MT4-MMP, which is increased upon stimulation with TNF-alpha. Consequently, MT4-MMP may be directly involved in the degradation of extracellular matrix components and/or modulate the activity of other proteins implicated in eosinophil migration and tissue remodeling.
Gauthier
Marie-Christine
MC
Institut Universitaire de Cardiologie et de Pneumologie de l'Université Laval, Que., G1V 4G5, Sainte-Foy, Canada.
Racine
Christine
C
Ferland
Claudine
C
Flamand
Nicolas
N
Chakir
Jamila
J
Tremblay
Guy M
GM
Laviolette
Michel
M
D002478:Cells, Cultured; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D007150:Immunohistochemistry; D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D009298:Nasal Polyps / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C402225:MMP17 protein, human; D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases