Adhesion molecules in lung diseases

The human body possesses highly specialized cellular defense mechanisms that, when activated pathologically, can induce a number of immunologic disorders. For a normal cellular immune response, the following conditions must be fulfilled: (1) accumulation of white blood cells, (2) their diapedesis through the vessel walls of the inflammatory area affected by an injurious agent, and (3) normal cellular effector functions in the tissue. This cascade of inflammatory processes has recently been shown to be regulated by a group of molecules that are termed adhesion molecules and consist of three subfamilies: selectins, the immunoglobulin supergene family, and integrins. The cellular functions influenced by adhesion molecules include, among others, cytotoxic T-cell responses, CD4-dependent activation of B lymphocytes by T lymphocytes, activation of granulocytes and macrophages, phagocytosis of opsonized particles by monocytes, macrophages, and granulocytes, antigen-presenting function of macrophages, their antibody-dependent cytotoxicity, initiation of a respiratory burst by white blood cells, and activation of fibroblasts. Studies performed in recent years have shown that pathogenetically relevant changes in the expression and function of adhesion molecules are involved in a variety of pulmonary diseases. These changes include the accumulation and activation of alveolar macrophages in smokers, experimentally induced bronchial hyperreactivity in bronchial asthma, accumulation of eosinophils in allergic rhinitis, bleomycin-induced pulmonary fibrosis, binding of viruses and bacteria to respiratory mucosa, and various mechanisms of acute damage to pulmonary parenchyma. Though their role in tumor development is still unclear, adhesion molecules are obviously involved in determining the route and organotropism of metastases. Further studies of the function of adhesion molecules in pulmonary diseases will contribute to our understanding of the pathomechanisms of these diseases and, through the development of specific antibodies, may provide attractive new therapeutic approaches to problems for which treatment is not yet available.