Increased intracellular activity of matrix metalloproteinases in neutrophils may be associated with delayed healing of infection without neutropenia in myelodysplastic syndromes.

Abstract

To investigate the influence of the intracellular activity of type II and type IV collagenases [matrix metalloproteinases (MMP)-2, MMP-8, and MMP-9] in neutrophils from patients with myelodysplastic syndromes (MDS), we tried to measure intracellular activity using flow cytometric techniques. We also studied the clinical features of patients showing high activity. The intracellular collagenase activity, expressed as a ratio to the standardized fluorescence intensity, in patients with MDS was significantly higher than normal volunteers (19.5+/-14.8 vs 13.3+/-6.8, p=0.024). The difference among subcategories of MDS according to the French-American-British (FAB) and WHO classifications was not significant. No significant influence of three variables of the International Prognostic Scoring System (IPSS) was seen on activity. Of 8 patients with activity of more than 26.9 (mean+2 standard deviations of normal controls), 5 experienced an episode of delayed healing of infection without neutropenia, while 1 of 43 patients with activity of less than 26.9 experienced such an episode (p=0.0002). The average collagenase activity of six patients with delayed healing of infection without neutropenia (44.7+/-28.9) was significantly higher than that of other MDS patients (16.0+/-7.1, p=0.005) (Fig. 4). It was also significantly higher than the activity of the control group (13.3+/-6.8, p=0.011). Our report suggests that increased collagenase activity in neutrophils may delay healing of infection. In addition, we suggest that increased collagenase activity may be an independent prognostic factor for the susceptibility to severe infection in MDS.