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Characterization of Serum Inhibitors of Neutrophil Chemotaxis Associated with Anergy¹

From the Departments of Medicine and Microbiology, University of New Mexico School of Medicine, Bernalillo County Medical Center, Albuquerque, New Mexico 87131

Abstract

Forty patients with acute illness and a leukocytosis of greater than 12,000 WBC/mm³ were studied with respect to skin test reactivity and plasma or serum chemotactic activity. Sixteen patients were skin test negative when tested with a battery of six common antigens capable of eliciting delayed-type skin test responses. Serum from 12 of these patients contained chemotactic inhibitors capable of abrogating chemotaxis toward purified C3_a, C5_a, and kallikrein in addition to normal and immune complex-activated human serum. All patients having inhibitor were skin test negative. The presence of chemotactic inhibitor in patient serum directly paralleled skin test anergy. After clinical improvement, patients became skin test positive to at least one of the six antigens used, and their serum simultaneously lost chemotactic inhibitor. Physical characteristics of a 50% ammonium sulfate-precipitated inhibitor included heat stability, mobility by zone electrophoresis, elution in the third peak from DEAE with a 0.1 M, pH 5.8, phosphate buffer, and sedimentation coefficients of 6.8 and 10.7S. Functional studies indicated that the inhibitor could not be absorbed by large numbers of leukocytes and could be neutralized by excess normal human serum. The serum chemotactic inhibitory activity and the highly significant association with skin test anergy indicate that chemotactic inhibitors may function as naturally occurring anti-inflammatory agents in patients with systemic illness.

Footnotes

¹ This work was supported by Grants AM 13824-04 and TO1-A100343-04 from the United States Public Health Service.

² Address reprint requests to: Dennis E. Van Epps, Ph.D., Fellow in Immunobiology, Department of Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131.