Integrins, macrophages, and sarcoidosis.

T he article by Striz et al in this issue of Chest (see page 882) examines @32 integrin and ICAM-1 ex pression on human alveolar macrophages in patients with sarcoidosis and in control subjects. To put this interesting article in context, a brief overview of the background leading to this work is necessary. The cell population recovered by bronchoalveolar lavage (BAL) from normal lungs is predominantly (>90 percent) alveolar macrophages in various stages of maturation. Small numbers of lymphocytes are also found. Pulmonary alveolar macrophages normally in gest and contain inhaled particulates without inducing local inflammation. Moreover, specific immune re sponses to inhaled antigens appear to be down regulated under normal circumstances.' For instance, alveolar macrophages facilitate lymphocyte prolifera tion to mitogen in vitro at low macrophage-lymphocyte ratios.2 However, at high macrophage-lymphocyte ra tios, like those in the lung and in BAL fluid, this proliferation is suppressed.3'@At least four mechanisms are thought to be involved in this down-regulation. Compared with blood monocytes or newly recruited lung monocytes, pulmonary alveolar macrophages demonstrate increased intracellular degradation (proc essing) and decreased cell surface display (presenta tion) of antigen,5 deficient production of the T-cell activator interleukin (IL)-1,6 active suppression of lymphocyte activation by the production of large quantities of prostaglandin E2 (PGE2),7 and decreased surface contact with T cells due to decreased expres sion ofsurface LFA-l, an alpha subunit of@32 integnns.8 Integrins are cell-surface glycoproteins, which fa cilitate cell adhesion to extracellular matrix proteins and ligands on other cells. More recently, they have been shown to play other roles, including involvement in cellular growth and differentiation. Integnns in elude at least 15 dipeptide transmembrane molecules, which have been divided into six subfamilies based on unique beta chains. Each of these associates non covalently with an alpha chain of one or more types. Integrins are found on many cells, including endothe hal cells, fibroblasts, and immunocompetent cells.@ Many of them have been characterized adequately enough to be given cluster designation (CD) nomen clature. The @32, or very late activation integrins, are widely distributed and facilitate adhesion to extracellular matrix proteins such as fibronectin and collagen. They are believed to be important in embryogenesis and wound healing.@ The @ or leukocyte, integrins are the best studied. The @32 (CD18) subunit associates with one of three cules are found on leukocytes and endothelial cells. CD18 is foundon the same cells, and binds to iC3b. Leukocyte integrins are …