Georg Kraal

In the present study, a set of three monoclonal antibodies is described, each of which recognizes cells of the monocyte-macrophage lineage in the rat. The tissue distribution, in particular in lymphoid organs, of each of the three monoclonals is determined by immunoenzyme histochemistry on cryostat sections, as well as on cell suspensions. Results show that ED1 recognizes a cytoplasmic antigen in monocytes and in most macrophages, free and fixed. ED2 and ED3 recognize membrane antigens of tissue macrophages, discriminating between distinct subpopulations of macrophages, each with a characteristic localization in the compartments of lymphoid organs. No other cell types except cells of the mononuclear phagocyte system are positive for any of the three monoclonals. Possible relations between the macrophages recognized by this set of monoclonals and dendritic cells are discussed.

Atherosclerosis is an inflammatory disease, characterized by the accumulation of macrophage-derived foam cells in the vessel wall and accompanied by the production of a wide range of chemokines, cytokines, and growth factors. These factors regulate the turnover and differentiation of immigrating and resident cells, eventually influencing plaque development. One of the key regulators of inflammation is the transcription factor nuclear factor kappaB (NF-kappaB), which, for a long time, has been regarded as a proatherogenic factor, mainly because of its regulation of many of the proinflammatory genes linked to atherosclerosis. NF-kappaB may play an important role in guarding the delicate balance of the atherosclerotic process as a direct regulator of proinflammatory and anti-inflammatory genes and as a regulator of cell survival and proliferation. Here we address recent literature on the function of NF-kappaB in inflammatory responses and its relation to atherosclerosis.

Class II major histocompatibility complex (Ia)-bearing dendritic cells (DC) from airway epithelium and lung parenchyma express low-moderate antigen presenting cell (APC) activity when freshly isolated. However, this function is markedly upregulated during overnight culture in a manner analogous to epidermal Langerhans cells. The in vitro "maturation" process is inhibited by coculture with pulmonary alveolar macrophages (PAM) across a semipermeable membrane, and the degree of inhibition achieved can be markedly increased by the presence of tumor necrosis factor alpha. In addition, PAM-mediated suppression of DC function is abrogated via inhibition of the nitric oxide synthetase pathway. Functional maturation of the DC is accompanied by increased expression of surface Ia, which is also inhibited in the presence of PAM. Prior elimination of PAM from DC donors via intratracheal administration of the cytotoxic drug dichloromethylene diphosphonate in liposomes, 24-72 h before lung DC preparation, achieves a comparable upregulation of APC activity, suggesting that (consistent with the in vitro data) the resident PAM population actively suppresses the APC function of lung DC in situ. In support of the feasibility of such a regulatory mechanism, electron microscopic examination of normal lung fixed by intravascular perfusion in the inflated state (which optimally preserves PAM in situ), revealed that the majority are preferentially localized in recesses at the alveolar septal junctions. In this position, the PAM are in intimate association with the alveolar epithelial surface, and are effectively separated by as little as 0.2 microns from underlying interstitial spaces which contain the peripheral lung DC population. A similar juxtaposition of airway intraepithelial DC is demonstrated with underlying submucosal tissue macrophages, where the separation between the two cell populations is effectively the width of the basal lamina.