Effects of heterologous antineutrophil serum in guinea pigs. Hematologic and ultrastructural observations.

Abstract

Two pools of rabbit anti-guinea pig neutrophil serum (ANS) were prepared using an intravenous (ANS I) or subcutaneous (ANS II) route of immunization with proteose peptone-stimulated peritoneal exudate neutrophils (PMNs) from albino guinea pigs. In vitro, both pools of ANS contained high titers of agglutinating antibodies to neutrophils and lower titers against lymphocytes and red cells. Agglutinins against all three cell types could be selectively removed by absorption. The in vivo hematologic effects of both the absorbed and unabsorbed antisera were examined after intraperitoneal administration, and the effects of ANS on neutrophils in blood, bone marrow, and peritoneal cavity were examined by light and electron microscopy of spleen, liver, lung, lymph node, buffy coat, bone marrow and pellets of peritoneal cells removed at various time intervals within 24 hours. Injection of either antisera caused a rapid decrease in circulating neutrophils and lymphocytes, which reached their lowest levels within 12 hours. Neutrophils that disappeared from the circulation were sequestered primarily in liver and spleen where they were phagocytized, as morphologically intact cells, by macrophages and then rapidly digested. Immature bone marrow neutrophils as young as early myelocytes were ingested by macrophages in the marrow at 6 hours or later after ANS. Neutrophils that were phagocytized were apparently opsonized by ANS since there was no ultrastructural evidence of neutrophil lysis in blood or bone marrow after ANS treatment. However, both lysed and ingested neutrophils were observed in the peritoneal cavity. Absorption of ANS with neutrophils removed the ability of the serum to produce neutropenia. However, absorption of ANS with lymphocytes did not alter the lymphopenia produced by the antiserum. The fate of lymphocytes leaving the peripheral circulation was not apparent. Lymphocytes did not accumulate in liver or spleen sinusoids and were not ingested by macrophages in these organs, as were the neutrophils. There was no evidence of paracortical depletion or extensive phagocytosis of lymphocytes in lymph nodes after ANS, as other investigators have reported after administration of antilymphocyte serum.