RESUMEN
Pulmonary alveolar macrophages (AMphis) are incompetent to phagocytose unopsonized Pseudomonas aeruginosa, but ingestion by other macrophage phenotypes (i.e., peritoneal macrophages) occurs efficiently. The purpose of this study was to explore factors that might control such phenotypic differences. Our laboratory has demonstrated that AMphis exposed to sodium azide display enhanced phagocytosis of P. aeruginosa. Here we report that the phagocytic-enhancing effect of sodium azide was abrogated by inhibitors of protein kinase C (PKC). Furthermore, the addition of PKC agonists, such as phorbol myristate acetate (PMA), and tumor necrosis factor alpha (TNF-alpha), mimicked the phagocytic enhancing effect of sodium azide. We conclude that AM4phis are normally incompetent to phagocytose P. aeruginosa. Factors that up-regulate AMphi function (azide, PMA, TNF-alpha) can reverse the phagocytic incompetence in vitro. Although these compounds are not appropriate candidate therapeutic agents, their effects provide insights for understanding of the pathways responsible for regulation of P. aeruginosa phagocytosis.
Asunto(s)
Macrófagos Alveolares/fisiología , Fagocitosis/fisiología , Proteína Quinasa C/fisiología , Pseudomonas aeruginosa/fisiología , Animales , Carcinógenos , Células Cultivadas , Activación Enzimática/efectos de los fármacos , Activación Enzimática/fisiología , Inhibidores Enzimáticos/farmacología , Macrófagos Alveolares/microbiología , Ratones , Fagocitosis/efectos de los fármacos , Azida Sódica/farmacología , Acetato de Tetradecanoilforbol/farmacología , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
Children with leukocyte adhesion deficiency type I are at risk for overwhelming infection because their neutrophils lack surface beta 2 integrins (CD18/CD11) that normally interact with endothelial cell adhesion molecules and mediate migration to sites of bacterial invasion. In vitro studies of phagocytic cells from an infant with leukocyte adhesion deficiency type I demonstrated that complement receptor 3 (CD18/CD11b) mediates nonopsonic phagocytosis of some Pseudomonas aeruginosa strains and might play a control role in the control of Pseudomonas infections at sites where there are low levels of opsonins.
Asunto(s)
Síndrome de Deficiencia de Adhesión del Leucocito/complicaciones , Fagocitosis/inmunología , Infecciones por Pseudomonas/complicaciones , Infecciones por Pseudomonas/inmunología , Antígenos CD18 , Humanos , Recién Nacido , Síndrome de Deficiencia de Adhesión del Leucocito/inmunología , Antígeno de Macrófago-1 , Pseudomonas aeruginosaRESUMEN
Complement receptor 3 (CR3) mediates both opsonic and nonopsonic phagocytosis of bacteria. Leukocyte adhesion deficiency (LAD) allows for the study of CR3-dependent phagocyte-bacterial ingestion, since LAD phagocytes do not express this receptor. Phagocytes from an infant with LAD were unable to ingest 50% of the Pseudomonas aeruginosa strains studied, which indicates a requirement for CR3. However, the remaining strains were phagocytosed in the absence of CR3, and ingestion was blocked by monoclonal antibodies directed at CD14. This CR3/CD14 receptor bias was further confirmed by using thioglycollate-elicited murine peritoneal macrophages, which have nonfunctional CR3 before activation. Results indicate that either CR3 or CD14 is involved independently in nonopsonic phagocytosis of different P. aeruginosa strains. Clearance of P. aeruginosa from the endobronchial space may be facilitated by nonopsonic phagocytosis, since low levels of opsonins are present. The impact of lung infection with P. aeruginosa may be determined, in part, by the phagocytic receptor that mediates ingestion.