Initiation and Maintenance of the Granulomatous Response

¹ The Department of Pathology and Division of Pulmonary and Critical Care, Department of Internal Medicine, The University of Michigan Medical School, Ann Arbor.

Granulomatous inflammation possesses a common set of pathologic events which appear to be due, at least in part, to the continued recruitment and activation of a variety of leukocyte populations. Although the initiating insult may vary, as in the etiology of tuberculosis, sarcoidosis, or berylliosis, the subsequent immune reaction, characterized by infiltrating leukocytes, is often the same. While the exact mechanism(s) by which leukocytes are elicited to the granuloma is not entirely understood, it is likely that the local production of specific chemotactic agents are paramount to the success of the developing lesion. The recent identification of a novel supergene family of chemotactic cytokines, which possess activity for eliciting specific leukocyte populations, has provided a potential mechanism for the constant leukocyte recruitment response associated with chronic inflammation. In addition, the expression of these chemotactic polypeptides has been identified in a number of cellular sources, including mononuclear leukocytes, fibroblasts, epithelial cells, smooth muscle cells, and endothelial cells. Studies directed at understanding the ongoing recruitment process which leads to the continued cellularity of a granulomatous lesion are likely to provide needed insight to develop more efficacious therapies to treat these chronic inflammatory diseases.