The structure of mononuclear phagocytes differentiating in vivo. II. The effect of Mycobacterium tuberculosis.

The development and resolution of granulomas induced by Mycobacterium tuberculosis were sequentially traced by correlated light and electron microscopy. The scattered, immature monocytes initially composing the lesions evolved by orderly steps into coalescent, well developed macrophages and ultimately into swirling nests of highly complex epithelioid cells. These ultrastructural changes represent differentiation in vivo of the mononuclear phagocytes. The number of mycobacteria present than waned markedly, and the epithelioid granulomas developed into foreign body granulomas and finally into simple chronic inflammation. Concmonitantly, the epithelioid cells evolved into macrophages and ultimately into immature, monocyte-like forms. These observations suggest that the development of a granuloma represents differntiation in vivo of the constituent mononuclear phagocytes in response to an evoking stimulus. From comparisons with previous studies, mononuclear differentiation in vivo appears to have a fixed pattern and a markedly alterable pace. The observations also suggest a previously undescribed fate for mononuclear phagocytes in developing granulomas. As the granuloma-evoking agent is destroyed, the highly differentiated mononuclear phagocytes change into less mature forms.