Kinetic studies of phagocytosis. IV. Cellular defects and humoral inhibition as causes of impaired neutrophil phagocytosis in sarcoidosis.
Kinetic measurements of the serum-independent uptake of IgG-coated or complement-opsonized latex particles have been performed in 58 patients with sarcoidosis. The mean rate for phagocytic uptake of IgG particles was 0·56 min-1 which was not different from that of the controls (0·59 min-1). The phagocytosis of complement-opsonized particles was in the patient group 0·53 min-1 and significantly (P<0·001) reduced compared to the rate of the controls (mean rate 0·94 min-1), indicating neutrophil C3b-receptor dysfunction in sarcoidosis. PMNs from patients with sarcoidosis were not stimulated by the presence of autologous serum in contrast to PMNs from normals and in individual cases even a reduced uptake was found. More than one-third of the sarcoid sera also inhibited the phagocytosis of normal PMNs indicating the presence of a phagocytosis-inhibitory activity in sarcoid sera. Patients with more severe lung affection as estimated by measurements of total lung capacity, central airway obstruction, small airway function and pulmonary X-ray changes had a more reduced PMN phagocytosis in the presence of autologous serum than those with minor signs of lung affection (P<0·05). The phagocytosis-inhibitory activity of sarcoid serum was also more pronounced in those individuals who had high pulmonary score (P<0·05) or radiographic stage II-IV sarcoidosis (P<0·01). No correlation was found between serum levels of lactoferrin or lysozyme and any of the phagocytic variables while elevated β2-microglobulin levels were associated with more pronounced serum-mediated inhibition of PMN phagocytosis (P<0·05). The relevance of these findings to the pathogenesis of granuloma formation in sarcoidosis is discussed.