Ectopic localization of matrix metalloproteinase-9 in chronic cutaneous wounds.

• It has been hypothesized that excessive activity of matrix metalloproteinases (MMPs), in particular the gelatinases MMP-9 and MMP-2, contributes to poor healing of chronic skin ulcers. We compared MMP-9 and MMP-2 in wound margin biopsies of standardized acute partial-thickness wounds in healthy volunteers (n = 6) and in venous leg ulcer patients (n = 12) with those of chronic wounds of different etiologies (n = 34) by a combination of specific analyses of activity and protein localization. We also studied MMP-14 by immunohistochemistry and in situ hybridization in parallel. Neither MMP-9 (P =.814) nor MMP-2 (P =.742) endogenous activities differed significantly between acute and chronic wound tissues. Acute wound healing was characterized by induction of MMP-9 in the advancing epithelium. In chronic wounds, prominent MMP-9 immunostaining was seen in neutrophils and macrophages in the ulcer bed, but virtually no MMP-9 was detected in wound edge keratinocytes. MMP-2 was increased and activated with acute wound age. MMP-2 was found abundantly in dermal fibroblasts and endothelial cells beneath, but not in new epithelium of acute and chronic wounds. MMP-14 mRNA or protein was detected solely in the stroma of both acute and chronic wounds. In conclusion, the overall activity of gelatinases MMP-9 and MMP-2 was not increased in chronic wounds compared to normally healing wound tissues. Chronic nonhealing wounds may not be caused by excessive gelatinase activity, but are distinguished from healing wounds by an unfavorable distribution and persistance of MMP-9.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Kirurgi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Surgery (hsv//eng)

Keyword

Gelatinase A : genetics

Female

Chronic Disease

Cultured

Cells

80 and over

Aged

Adult

Acute Disease

Leg Ulcer : pathology

Male

Metalloendopeptidases : genetics

Metalloendopeptidases : metabolism

Middle Age

Messenger : metabolism

RNA

Skin : enzymology

Skin : injuries

Skin : pathology

Support

Non-U.S. Gov't

Wounds and Injuries : pathology

Wound Healing : physiology

Wounds and Injuries : enzymology

Gelatinase A : metabolism

Gelatinase B : genetics

Gelatinase B : metabolism

Human

Immunohistochemistry

In Situ Hybridization

Leg Ulcer : enzymology

Publication and Content Type

art (subject category)

ref (subject category)