Gelatinase B or matrix metalloproteinase-9 is involved in inflammation and in autoimmuneand vascular diseases. In contrast to t
he constitutive and
homeostatic matrix metalloproteinase-2, matrixmetalloproteinase-9 is an inducible enzyme. Furt
hermore, it needs tig
ht regulation, and a major controlmec
hanism of its enzymatic activity is t
he activation of t
he latent enzyme by proteolysis of t
he 87 residuepropeptide. Activated matrix metalloproteinase-9 is detected in many vascular or
hematological diseasestates, including in an experimental model for cerebral malaria wit
h Plasmodium berghei ANKA. However,insig
ht into its activation mec
hanism is incomplete. In view of t
he association wit
h hemorr
hagic and
hemolytic diseases, it was studied w
het
her and
how
hemoglobin and its derivatives mig
ht activate pro-matrix metalloproteinase-9. Incubation of matrix metalloproteinase-9 wit
h hemin or
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hematin, t
he coreconstituent of
hemozoin or malaria pigment, leads to differential autocatalysis of t
he propeptide, mediatedby allosteric interaction wit
h t
he
hemopexin domain. T
he cleavage catalyzed by
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hematin coincideswit
h t
he first cleavage by stromelysin-1/matrix metalloproteinase-3, and preincubation of matrixmetalloproteinase-9 wit
h ![](/images/gifc<font color=)
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hematin en
hances t
he activation rate by matrix metalloproteinase-3 at least6-fold. T
hese findings suggest t
hat reduction of
hemorr
hage and
hemolysis mig
ht prevent matrixmetalloproteinase-9-mediated inflammatory and vascular damages.