Matrix metalloproteinases and TIMP‐1 production by peripheral blood granulocytes from COPD patients and asthmatics

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Abstract
Both asthmatic and COPD patients were found to have increased amounts of granulocytes and matrix metalloproteinase‐9 (MMP‐9) in their sputum. The present study was conducted to investigate whether the elevated amounts of MMP‐9 and TIMP‐1 found in such patients' airways may be linked to an enhanced secretion by granulocytes. Blood granulocytes from asthmatics (n=10), COPD patients (n=11), and healthy controls (n=11) were isolated and cultured under basal conditions or after stimulation by phorbol 12‐myristate 13‐acetate (PMA) or N‐formyl‐l‐methionyl‐l‐leucyl‐l‐phenylalanine (fMLP). MMP‐9 activity was detected by zymography while MMP‐8 and TIMP‐1 levels were measured by ELISA. In zymography, pro‐ and activated forms of MMP‐9 were present in each group (healthy subjects, asthmatics, and COPD patients). Spontaneous release was not different between the three groups. Stimulation by fMLP and PMA increased to a similar extent the release of MMP‐9 by granulocytes in all the three groups. TIMP‐1 levels were also increased after stimulation by PMA and fMLP only in healthy subjects and COPD patients. MMP‐8 levels were barely detectable. We conclude that circulating granulocytes from COPD patients and asthmatics do not display an abnormal secretion of MMP‐9, and that granulocytes from asthmatics have an impaired ability to release TIMP‐1 upon stimulation.