Mononuclear cell turnover in chronic inflammation: studies on tritiated thymidine-labeled cells in blood, tuberculin traps, and dermal BCG lesions of rabbits

Abstract

Rabbits were injected intradermally in multiple sites with BCG. Four days after the BCG injection, they were injected intravenously with a single pulse of tritiated thymidine (3H-TdR) at various times thereafter, the BCG lesions were biopsied and evaluated for 3H-TdR-labeled mononuclear cells (MN). Periodically, Old Tuberculin (OT) was injected intradermally, creating MN traps which were biopsied and evaluated 1 day after their onset. 3H-TdR-labeled cells were also evaluated in samples of blood. During the first 8 days after the 3H-TdR pulse, the labeled MNs represent short-lived cells, i.e., recently dividing monocytes and lymphocytes. During this time, the percentage of labeled MNs in the blood, in the traps, and in the BCG lesions rose and fell together. This result suggests that the majority of the MNs in the BCG lesions had a turnover rate of about a week. By 12 days and afterward, the percentage of MNs labeled by 3H-TdR in the blood was higher than that in the BCG lesions which was in turn higher than that in the traps. At this time the circulating MN population probably contained labeled long-lived lymphocytes that did not enter inflammatory sites (the traps) as readily as the short-lived lymphocytes. The labeled MNs remaining in the BCG lesions probably did not divide and dilute out their 3H-TdR label as readily as those that were trapped from the bone marrow via the blood. The percentage of MNs labeled with 3H-TdR in the traps had decreased to about one-fifteenth of its peak value by 12 days, suggesting that the bone marrow's supply of labeled MNs was depleted at this time, except for the few cells labeled as a result of 3H-TdR reutilization.