THE DISCHARGE OF GRANULOCYTES FROM GUINEA PIG MARROW IN RESPONSE TO INTRAVENOUS T. A. B. VACCINE: A QUANTITATIVE STUDY

The history of leucocytosis is long, and the literature pertaining to it, voluminous. The term, “leucocytosis,” was first used by Virchowl in 1860, and in Lecture 111 of his Zellularpathologie he drew a distinction between leucocytosis and leukemia. The introduction of the differential staining of leucocytes by Ehrlich2 in 1879 greatly stimulated the study of leucocytosis. L o ~ i t t , ~ and Goldscheider and Jacob4 injected various organic substances, organ extracts, and bacteria into rabbits, and subsequently observed the peripheral white-cell count. In most cases, an initial leucopenia was followed by leucocytosis. Ehrlich and Lazarus5 emphasized that polymorphs were formed in the bone marrow, were motile and subject to chemotaxis. Muifl confirmed that leucocytosis was a function of bone marrow and was preceded by initial leucopenia. He noted an increased mitotic rate in the myelocytes for several days after the initial stimulus. He also concerned himself with the puzzling problem of the fate of the leucocytes which disappeared from the blood. He could not detect any histological change in the spleen, and postulated that they were sequestrated in the lungs. Doan and Zerfass and Doan, Zerfas et ~ l . , ~ again studied the nowfamiliar picture of initial leucopenia and secondary leucocytosis. They found that during the leucopenia phase there was an accumulation of polymorphs in the spleen, and abolished the leucopenia by preliminary splenectomy. They concluded that staphylococci and streptococci exerted both chemotactic and maturational effects on the bone marrow, whereas typhoid bacilli exerted only a chemotactic action. Farr and Lequireg further analyzed the changes following intravenous typhoid vaccine in rabbits. Craddock, A d a m et al.l0 and Craddock, Perry et al.” introduced the technique of leucopheresis and isotopic labeling to study leucocyte discharge from the marrow pool, which had been estimated by Yoffey12J3 (1954, 1955) to be 100 times larger than that of the peripheral blood in guinea pigs. Patt et a1.l4 employed essentially the same approach, removing leucocytes from the blood and observing their return to it. Perry et used typhoid vaccine and P32-labeling to study granulopoiesis. BiermanIsJ7 et al. made careful studies of the effects of leucopheresis in man. Athens et al.l8 followed the fate of leucocytes which had been labeled in vitro with DFP32 and then returned to the circulation. Gordon et al.lg used parabiotic rats, and found that leucopheresis in one induced leucocytosis in the other, presumably through the formation of a Leucocytosis-Inducing Factor (LIF) which was shown to produce discharge of granulocytes from the isolated limb perfused with plasma which contained it. Our own investigations have been directed to a quantitative study of the marrow in the intact animal. After confirming the large myeloid reserve of normal guinea pig marrow, it was noted by Harris et ~ 1 . 2 ~ that four hours after the administration of Leucocytosis-Promoting Factor (LPF) , a significant num-