HUMAN ALVEOLAR MACROPHAGES INHIBIT IMMUNOGLOBULIN PRODUCTION IN RESPONSE TO DIRECT B-CELL MITOGEN

B lymphocytes are crucial participants in pulmonary immune defense. Ho wever, excess local antibody production is associated with accelerated lung destruction in several types of lung disease. The purpose of the current study was to study the potential role of alveolar macrophages (AM) in the local regulation of immunoglobulin (Ig) production in the lung in response to a direct B cell mitogen, Staphylococcus aureus Co wan strain (SAC). AM, when added to peripheral blood mononuclear cells , caused a dose-dependent inhibition of IgG and IgM, while not affecti ng IgA production in response to SAC. The mechanism of the AM-induced inhibition included both membrane-bound and soluble signals. The inhib ition was not abrogated by indocin and catalase, or reversed by blocki ng antibodies to transforming growth factor-beta or interferon-gamma. Mononuclear cells isolated from human lung parenchyma displayed a redu ced response to SAC compared with blood cells. However, depletion of m acrophages from the parenchymal cells was associated with a restoratio n of IgG production in response to SAC. The results demonstrate that A M inhibit B cell responses to direct B cell mitogen and suggest that t he effect of AM is selective for IgM and IgG.