title: Macrophage inflammatory protein-1alpha C-C chemokine in parapneumonic pleural effusions.
abstract: Parapneumonic pleural effusions are associated with the presence of a variety of inflammatory cells whose influx into the pleural space is attributed to the presence of inflammatory cytokines. Macrophage inflammatory protein-1alpha (MIP-1alpha), an important mononuclear chemokine, plays a critical role in pulmonary parenchymal inflammatory disease, but its role in the recruitment and activation of mononuclear phagocytes in the pleural space is unknown. In this study we demonstrate that complicated parapneumonic pleural effusions (empyema) and uncomplicated parapneumonic pleural effusions contain significantly (P < .001) higher levels of MIP-1alpha with higher numbers of mononuclear cells when compared with effusions resulting from malignancy and congestive heart failure. The MIP- 1alpha was biologically active and contributed 43% and 37% of the mononuclear chemotactic activity of complicated and uncomplicated parapneumonic pleural fluids, respectively. In vitro, human mesothelial cells, when stimulated with interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), or bacterial lipopolysaccharide (LPS), produced MIP-1alpha. Northern blot analysis confirmed that both endogenous (IL-1beta or TNF-alpha) and exogenous (LPS) factors induce MIP-1alpha expression in mesothelial cells. Supernatants from activated mesothelial cells demonstrated chemotactic activity for mononuclear cells. This activity was blocked by MIP-1alpha antibody, indicating that the MIP-1alpha released was biologically active. We conclude that in parapneumonic pleural effusions, MIP-1alpha plays a major but not exclusive role in the recruitment of mononuclear leukocytes from the vascular compartment to the pleural space, and pleural mesothelial cells by production of MIP-1alpha actively participate in this process.
authors.affiliation: Department of Medicine, Veterans Affairs Medical Center, Indiana University School of Medicine, Indianapolis 46202, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Mohammed
authors.forename: N
authors.initials: N
authors.lastname: Nasreen
authors.forename: M J
authors.initials: MJ
authors.lastname: Ward
authors.forename: V B
authors.initials: VB
authors.lastname: Antony
mesh_terms: D002452:Cell Count; D002478:Cells, Cultured; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D006333:Heart Failure / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000378:metabolism*; D010996:Pleural Effusion / Q000378:metabolism* / Q000473:pathology; D018410:Pneumonia, Bacterial / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D054405:Chemokine CCL3; D054407:Chemokine CCL4; D017077:Culture Media, Conditioned; D007375:Interleukin-1; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha