title: Immunophenotyping of macrophages in human pulmonary tuberculosis and sarcoidosis.
abstract: Classic studies of tuberculosis (TB) revealed morphologic evidence of considerable heterogeneity of macrophages (MØs), but the functional significance of this heterogeneity remains unknown. We have used newly available specific antibodies for selected membrane and secretory molecules to examine the phenotype of MØs in situ in a range of South African patients with TB, compared with sarcoidosis. Patients were human immunodeficiency virus-negative adults and children, and the examined biopsy specimens included lung and lymph nodes. Mature pulmonary MØs (alveolar, interstitial, epithelioid and multinucleated giant cells) selectively expressed scavenger receptor type A and a novel carboxypeptidase-like antigen called carboxypeptidase-related vitellogenin-like MØ molecule (CPVL). CPVL did not display enhanced expression in sarcoidosis, vs. TB patients, as observed with angiotensin-converting enzyme (ACE), a related molecule. Immunocytochemical studies with surfactant proteins (SP)-A and -D showed that type II alveolar cells expressed these collectins, as did MØs, possibly after binding of secreted proteins. Studies with an antibody specific for the C-terminus of fractalkine, a tethered CX3C chemokine, confirmed synthesis of this molecule by bronchiolar epithelial cells and occasional endothelial cells. These studies provide new marker antigens and extend previous studies on MØ differentiation, activation and local interactions in chronic human granulomatous inflammation in the lung.
authors.affiliation: Department of Medical Biochemistry, Tygerberg Medical School University of Stellenbosch, Tygerberg, South Africa.
authors.forename: Lee-Anne
authors.initials: LA
authors.lastname: Stanton
authors.forename: Gael
authors.initials: G
authors.lastname: Fenhalls
authors.forename: Andrew
authors.initials: A
authors.lastname: Lucas
authors.forename: Peter
authors.initials: P
authors.lastname: Gough
authors.forename: David R
authors.initials: DR
authors.lastname: Greaves
authors.forename: James A
authors.initials: JA
authors.lastname: Mahoney
authors.forename: Paul van
authors.initials: Pv
authors.lastname: Helden
authors.forename: Siamon
authors.initials: S
authors.lastname: Gordon
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis; D002268:Carboxypeptidases / Q000378:metabolism; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D037662:Pulmonary Surfactant-Associated Protein A / Q000378:metabolism; D037663:Pulmonary Surfactant-Associated Protein D / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D017565:Sarcoidosis, Pulmonary / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D002268:Carboxypeptidases; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D008565:Membrane Proteins; D007703:Peptidyl-Dipeptidase A; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C515538:CX3CL1 protein, human; C515539:Cx3cl1 protein, mouse; C454739:Scarb1 protein, mouse