A B S T R A C T The phagocytic, bactericidal, and metabolic capabilities of circulating blood leukocytes from three adults (two males, one female) with hypogammaglobulinemia and recurrent pneumonia, chronic sinusitis, and intestinal giardiasis were studied. These functions were found to be normal when leukocytes from the patients were incubated in media containing normal human serum. Phagocytosis of Staphylococcus albus and polystyrene balls by both patient and normal leukocytes was diminished when the cells were incubated in hypogammaglobulinemic plasma. A similar defect in opsonization by patient plasma was also noted for pneumococci, Escherichia coli and variably with Staphylococcus aureus. Both patient and normal sera had equivalent levels of heat-labile S. albus opsonins; normal serum, however, contained heat-stable S. albus-specific absorbable opsonins in significantly greater quantities to account for its superior opsonic capacity. The addition of commercial gamma globulin or purified IgG to hypogammaglobulinemic sera restored full S. albus opsonic activity. The relevancy of these observations to the impaired host defenses in these patients will be discussed.
The bactericidal and metabolic activities of peripheral leukocytes obtained by dextran sedimentation from six patients with eosinophilia (50%-90%) due to a variety of etiologies were compared to cells collected from normal donors (70%-95% polymorphonuclear leukocytes). Eosinophils exhibited less phagocytosis than granulocytes, which appeared to account for diminished bactericidal activity against S. albus, S. aureus, and E. coli. The oxidation of glucose-1-14C, glucose-6-14C, and formate-14C were all significantly greater by nonphagocytizing eosinophils than neutrophils. With phagocytosis the increase in glucose-1-14C and glucose-6-14C oxidation was greater for eosinophils than neutrophils despite less measurable particle ingestion. The oxidation of formate-14C by phagocytizing eosinophils was similar to neutrophils in two patients studied. Leukocytic pyrogen (LP) was produced by phagocytosis of heat-killed S. albus or exposure to endotoxin in four out of five cases studied. Blood cells obtained from the fifth patient who had a probable myeloproliferative disorder did not produce significant amounts of LP when similarly stimulated. The common feature of diminished phagocytic activity and elevated resting oxidative metabolism in all patients regardless of etiology of the eosinophilia suggest that this property is common to all eosinophils. The failure of the morphologically abnormal eosinophils of the last patient to release LP served as another distinguishing feature of his cells and may be common to myeloproliferative disorders of the granulocyte series in general.
The administration of cobra venom factor or soluble human serum albumin (HSA)-anti-HSA complexes in antigen excess to rabbits resulted in a lowering of total hemolytic complement and C3 titers which persisted more than 24 hr. When such animals were challenged with complexes made up in 10 times antigen excess, the consumption of complement, febrile and thrombocytopenic responses were significantly diminished from those seen in untreated controls, and the duration of post-challenge leukopenia was shortened. These observations suggest a role for complement consumption, particularly of components C3-9, in the manifestation of these responses. Pyrogenic tolerance to complexes could not be explained by their more rapid removal from the circulation or a failure of the thermoregulatory centers to respond to preformed leukocytic pyrogen, suggesting that impairment in complement consumption either by depletion of C3 or interference with the activation of C1 might be responsible for this state. In contrast to these findings using complexes in 10 times antigen excess, similar prior treatment of immunized rabbits given HSA or of normal rabbits that received a mixture of soluble and insoluble complexes in 3 times antibody excess failed to suppress febrile or hematologic responses. If the formation of antigen-antibody complexes is essential for the production of these responses in immunized animals challenged with specific antigen, it appears that the large, rapidly-cleared complexes formed near equivalence are most likely involved in producing these biologic activities. Whereas some of the properties of these complexes make them more able to fix complement in vitro, it seems unlikely that complement-mediated mechanisms are significantly involved in the pathogenesis of the in vivo responses measured in these investigations.
Non-pyrogenic human serum albumin (HSA) administered to specifically immunized rabbits or given as HSA-anti HSA complexes to normal recipients induced fever, leukopenia, thrombocytopenia and consumption of complement. The pattern of these responses was distinctive from those induced by endotoxin of comparable pyrogenicity. Whereas the degree of in vitro complement consumption related directly to the antigen-antibody ratio, that observed in vivo after complex administration was more dependent upon the quantity of complexes given and their duration in the circulation. The rate of clearance of complexes from the circulation was independent of the degree of complement consumption but dependent upon the antigen-antibody ratio of the complexes. In general, no correlation was found between the extent of in vivo complement consumption and the degree or duration of fever, leukopenia or thrombocytopenia, although at low dosages the degree of complement consumption paralleled febrile responses.
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