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Macrophage Accumulation, Division, Maturation and Digestive and Microbicidal Capacities in Tuberculous Lesions

II. Rate at Which Mononuclear Cells Enter and Divide in Primary BCG Lesions and Those of Reinfection¹

From the Department of Radiological Science, School of Hygiene and Public Health, and the Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21205

Abstract

During the first 2 weeks the rate of entry of mononuclear cells (MN) into rabbit dermal BCG lesions was roughly proportional to the increase in size of the lesions. Lesions of reinfection increased in size much faster than primary lesions.

After caseous necrosis was prominent, changes in lesion size no longer reflected the entry of new MN because many were dying. Tritiated thymidine (H³T) was therefore used to label MN (mostly in the bone marrow), and their rate of entry into dermal BCG lesions was determined by autoradiographic techniques. Multiple lesions were produced and biopsied, each at a different time after a single intravenous (i.v.) pulse of H³T. This pulse was given when the BCG lesions were -1, +6, +14 or +27 days of age. Five days afterward 20 to 30% of the MN present were labeled, regardless of whether the lesion was beginning (-1 and +6 days), at its height (+14 days) or regressing (+27 days). Thus there was a continuous entry of new MN into the lesions throughout their life. Many more H³T-labeled MN entered the BCG lesions after hypersensitivity to tuberculin developed.

The rate of local MN division in dermal BCG lesions was determined by H³T grain count analyses. A single i.v. pulse of H³T was given to rabbits when their lesions were -1, +6, +14 or +27 days of age, and biopsies were made 1, 2, 5 and 8 days after the pulse. The reduction in H³T grain counts caused by previous MN division in the bone marrow was compared with the grain count reduction caused by MN division in the BCG lesions. The rate of MN division in these lesions was highest when delayed hypersensitivity was strong, namely in lesions of reinfection and in 14-day primary lesions.

Similar H³T grain count analyses indicated that the MN which divided in the BCG lesions did so only once (or twice) during their first week of residence. After such division, they still functioned awhile before they died and were replaced by new MN from the bloodstream. Thus most of the MN in tuberculous lesions were relatively recent immigrants, and their local division did not contribute substantially to the total number present.

Footnotes

¹ Supported by Grant AI-08876 from the United States-Japan Cooperative Medical Science Program of the National Institute of Allergy and Infectious Diseases, United States Public Health Service; Grant HE-14153 from the National Heart and Lung Institute, United States Public Health Service, for the Johns Hopkins Specialized Research Center on Lung; and by a contract with the Defense Atomic Support Agency and the Army Medical Research and Development Command.

² Dr. Ando and Dr. Shima are on leave of absence from the First Department of Internal Medicine, Kumamoto University School of Medicine, Kumamoto, Japan.

³ Address reprint requests to Dr. Arthur M. Dannenberg, Jr., Johns Hopkins School of Hygiene and Public Health, 615 North Wolfe Street, Baltimore, Marvland 21205.