A Novel Neutrophil (PMN) Dysfunction Syndrome: Infections and Poor Wound Healing Associated with Defective Motility but Normal Expression and Function of CD11b

Abstract 878 Hematology-Oncology II Poster Symposium, Sunday, 5/2

Patients with deficiency of PMN function such as leukocyte adhesion deficiency (LAD) exhibit a propensity to bacterial infections and defective wound healing. We present a patient with clinical complications similar to those seen with LAD but normal expression and function of CD11b. The patient had delayed umbilical cord separation at 1 mos. of age and, at 5 wks, developed a perirectal abscess which did not heal in spite of incision, drainage and IV antibiotics. Wound debridement demonstrated tissue necrosis and no pus. At 8 wks, the patient developed a periumbilical abscess and peritonitis. The patient received 8 WBC transfusions over 10 days and IV antibiotics with resolution of his umbilical wound and improvement of the perirectal abscess. Assessment of the patient's PMNs showed a severe motility defect in a modified Boyden chamber; cells failed to migrate into the filter with buffer and exhibited deficient migration (20-25% of control) in response to zymosan activated serum. Bactericidal activity to S. Aureus by patient's PMNs was mildly reduced compared to control. PMNs isolated from the patient and control were evaluated for superoxide anion (O₂^-) measured as SOD inhibitable cytochrome c reduction, CD11b expression with flow cytometry, and actin assembly with NBD phallicidin in response to a variety of agonists. Shown below are results for O₂^-. (Table)

Table 1 No caption available.

Patient's PMNs demonstrated normal O₂^- production in response to PMA (200ng/ml) and opsonized zymosan (OZ, 1mg/ml) but no activity with fMLP (1µM) or PAF/fMLP (1µM/1µM). Expression of CD11b by resting PMNs or cells stimulated with PMA, fMLP or PAF was comparable to control values. Finally, actin assembly in patient's PMNs was blunted compared to control PMNs (ratio, stimulated/resting values: 1.98-2.16 for controls with fMLP and PMA vs 1.30-1.41 for the patient). This patient exhibited a neutrophil chemotactic defect and clinical course similar to those of LAD, but CD11b expression and function were normal. The results for functional and biochemical responses to standard agonists represent a novel syndrome of PMN dysfunction and suggest a defect in signaling pathway(s) critical to some PMN functions.