Pneumococcal sonicate-induced biphasic granulocytopenia and its dissociation from pulmonary leukostasis. The contribution of pneumococcal products and complement to early and late granulocytopenic phases.
The pathogenesis of pneumococcus (PNC)-induced granulocytopenia is unclear. We studied its relationship to pulmonary leukostasis and the possible roles of PNC constituents and complement. Nonviable PNC was infused into normal and 99% C3-depleted rabbits. PNC challenge induced both granulocytopenia and pulmonary leukostasis in normal animals; complement-depleted animals displayed granulocytopenia without pulmonary leukostasis. Therefore an intact complement system was not essential to the granulocytopenia, whereas pulmonary leukostasis was complement-dependent. Rabbits infused with serum, plasma, or nonpyrogenic normal saline, each after in vitro incubation with PNC, developed significant granulocytopenia (p less than 0.001, p less than 0.01, and p less than 0.001, respectively) with maximal mean percent decreases of -98%, -97%, and -91%, respectively. When the animals were sacrificed at 3 hr, no pulmonary leukostasis was found. The granulocytopenia persisted for 3 hr after infusion of either PNC-exposed serum or plasma, whereas the granulocytopenia induced by PNC-exposed saline was of less than or equal to 1 hr duration. If serum or plasma complement was inactivated prior to PNC incubation, subsequent infusion also induced significant granulocytopenia of less than 1 hr duration (p less than 0.05 and p less than 0.01). PNC-exposed saline that was subsequently heat-treated induced this same early (less than or equal to 1 hr) granulocytopenia (p less than 0.05). Control animals infused with serum, plasma, or saline unexposed to PNC displayed neither granulocytopenia nor pulmonary leukostasis. Therefore neither prior in vitro complement inactivation nor heat treatment after PNC incubation prevented the early granulocytopenic phase; in vitro complement inactivation totally aborted the late phase. The complement-independent, heat-stable early granulocytopenic phase was further investigated. Its granulocytopenia-inducing activity did not require the presence of PNC capsular polysaccharide and was resistant to trypsin treatment. With ultrafiltration, its molecular weight was 100,000 to 300,000. Thus PNC-induced granulocytopenia is a multifactorial phenomenon involving both complement-dependent and complement-independent mechanisms as well as contribution by PNC constituents or by-products.
D000380:Agranulocytosis / Q000209:etiology / Q000382:microbiology*; D000818:Animals; D003165:Complement System Proteins / Q000172:deficiency / Q000502:physiology*; D006358:Hot Temperature; D007962:Leukocytes / Q000502:physiology*; D008168:Lung / Q000098:blood supply* / Q000473:pathology; D011008:Pneumococcal Infections / Q000097:blood* / Q000150:complications / Q000276:immunology; D011817:Rabbits; D013010:Sonication; D013296:Streptococcus pneumoniae / Q000276:immunology; D014357:Trypsin / Q000494:pharmacology; D014462:Ultrafiltration
D003165:Complement System Proteins; D014357:Trypsin