Tissue-Specific Fc γ and Complement Receptor Expression by Alveolar Macrophages Determines Relative Importance of IgG and Complement in Promoting Phagocytosis of Pseudomonas aeruginosa

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Abstract

ABSTRACT

Because the expression of IgG Fc receptors and complement receptors on macrophages may vary in a tissue-specific manner, we used monoclonal antibodies and flow cytometry to define the expression and function of opsonin receptors on fresh normal and cystic fibrosis (CF) bronchoalveolar lavage (BAL) macrophages. Using flow cytometry to separately analyze individual types of cells, we then determined the relative contributions of IgG and complement to phagocytosis of Pseudomonas aeruginosa by fresh BAL cells, avoiding alterations in receptor expression due to in vitro purification or culturing techniques. Neither normal nor CF BAL macrophages express appreciable amounts of the complement receptors CRI, CR2, or CR3. These results were confirmed by immunohistochemical staining of fixed lung sections. BAL macrophages express a high-affinity IgG receptor, Fc γRI, that is not found on neutrophils (PMN). In contrast, chemoattractant-stimulated blood PMN express large amounts of CR1 and CR3 but do not express Fc γRI. These results correlate with phagocytosis assays, which show that phagocytosis by macrophages is enhanced by relatively low concentrations of IgG but that the addition of complement does not further increase their phagocytosis. In contrast, low concentrations of IgG alone do not promote phagocytosis by PMN, whereas addition of complement markedly enhances phagocytosis by PMN. These results may explain the previously reported sensitivity of macrophages rather than PMN to the “blocking” effects of anti-Pseudomonas antibodies from CF patients, and emphasize the pathologic significance of interference with IgG and complement mediated opsonization in the lung in CF.

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