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Abnormal granulocyte chemotaxis has been described in chronic hemodialysis patients. In this study, sera from 53 hemodialysis patients were tested for chemotactic inhibitory activity by a modified Boyden technique. Chemotactic inhibitory activity, defined as &gt;20% inhibition of normal granulocyte chemotaxis, was found in 45% of patients. Only sera from patients having undergone &gt;3 mo hemodialysis displayed chemotactic inhibitory activity and retained this inhibitory activity when retested 9 mo later. Four of five patients who had initially undergone &lt;3 mo hemodialysis and lacked serum chemotactic inhibitory activity developed inhibitory activity when tested 9 mo later. Clinical evaluation of patients with serum chemotactic inhibitory activity showed that these patients did not have a significantly increased incidence of infection, although a trend toward decreased mortality during the time of study was observed (P = 0.0721). Serum chemotactic inhibitory activity was heat stable at 56 degrees C for 30 min and concentration dependent. The major inhibitory component was found to have a sedimentation coefficient of 4S by sucrose density gradient centrifugation. The chemotactic inhibitory activity was not precipitated by 30% ammonium sulfate, but was partially precipitated by 50% ammonium sulfate. Inhibitory sera effectively suppressed neutrophil migration in response to chemotactic C5 fragment and Escherichia coli derived chemotactic factor but was least effective in a system mediated by casein. Furthermore, normal neutrophils preincubated in hemodialysis patient sera displayed normal chemotactic responsiveness indicating a lack of cell-directed inhibition. Serum fractions that contained the inhibitor were found to directly act on the chemotactic C5 fragment, reducing its chemotactic activity. This study indicates that a circulating 4S, heat-stable, factor-directed inhibitor of granulocyte chemotaxis is present in the sera of many hemodialysis patients and probably results from the hemodialysis procedure.

Serum Inhibitor of C5 Fragment-Mediated Polymorphonuclear Leukocyte Chemotaxis Associated with Chronic Hemodialysis