title: Vitronectin, fibronectin, and gp120 antibody enhance macrophage release of TNF-alpha in response to Pneumocystis carinii.
abstract: Alveolar macrophages (AMS) initiate inflammation during Pneumocystis carinii pneumonia by releasing cytokines including TNF-alpha. Recent studies suggest that macrophage responses to P. carinii are enhanced by serum opsonization, but the mechanisms of enhancement are not well defined. To determine whether macrophage release of TNF-alpha in response to P. carinii was augmented by immune opsonization, alveolar macrophages obtained from rabbits were cultured with P. carinii that had been opsonized with either nonimmune rabbit serum, immune serum generated against P. carinii, or an affinity-purified polyclonal Ab recognizing the major P. carinii surface Ag gp120. Each experiment also included organisms maintained in media alone (nonopsonized P. carinii). Opsonization of P. carinii with immune serum or gp120 Ab significantly enhanced macrophage TNF-alpha release. Interestingly, however, opsonization with nonimmune serum also increased TNF-alpha response to the organism. Because P. carinii is known to interact with the adhesive glycoproteins, vitronectin (VN) and fibronectin (FN), we hypothesized that they might also augment TNF-alpha release. Opsonization of P. carinii with VN or FN resulted in significant potentiation of macrophage TNF-alpha liberation. We further determined that VN and FN were present in increased quantities in the lower respiratory tract of patients with P. carinii pneumonia compared with normal volunteers. Additionally, VN and FN were demonstrated on the surface of freshly isolated P. carinii organisms by immunoblot analysis. Our study suggests that immune and nonimmune opsonins contribute to host defenses during P. carinii pneumonia by enhancing regional TNF-alpha release in response to the organism.
authors.affiliation: Thoracic Diseases Research Unit, Mayo Clinic and Foundation, Rochester, MN 55905.
authors.forename: L W
authors.initials: LW
authors.lastname: Neese
authors.forename: J E
authors.initials: JE
authors.lastname: Standing
authors.forename: E J
authors.initials: EJ
authors.lastname: Olson
authors.forename: M
authors.initials: M
authors.lastname: Castro
authors.forename: A H
authors.initials: AH
authors.lastname: Limper
mesh_terms: D000818:Animals; D000908:Antibodies, Fungal / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D005353:Fibronectins / Q000276:immunology / Q000378:metabolism; D005656:Fungal Proteins / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D016676:Macrophages, Alveolar / Q000276:immunology*; D009895:Opsonin Proteins / Q000276:immunology; D011010:Pneumocystis / Q000276:immunology* / Q000378:metabolism; D011020:Pneumonia, Pneumocystis / Q000276:immunology / Q000378:metabolism; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D019096:Vitronectin
chemical_list: D000908:Antibodies, Fungal; D005353:Fibronectins; D005656:Fungal Proteins; D006023:Glycoproteins; D009895:Opsonin Proteins; D014409:Tumor Necrosis Factor-alpha; D019096:Vitronectin