title: Expression and function of the C5a receptor in rat alveolar epithelial cells.
abstract: Although alveolar epithelial cells (AEC) form an important barrier for host defenses in the lung, there is limited information about ways in which AEC can directly participate in the lung inflammatory response. In the current studies, primary cultures of rat AEC (RAEC) have been shown to specifically bind recombinant rat C5a at high affinity and in a saturable manner. This binding was enhanced in a time-dependent manner by pre-exposure of RAEC to LPS, IL-6, or TNF-alpha, the increased binding of C5a being associated with increased levels of mRNA for the C5a receptor (C5aR). Exposure of RAEC to C5a also caused increased expression of mRNA for C5aR. As compared with exposure of RAEC to LPS or to C5a alone, exposure to the combination caused enhanced production of TNF-alpha, macrophage inflammatory protein-2, and cytokine-induced neutrophil chemoattractant-1, as well as increased intracellular levels of IL-1beta. These data indicate that RAEC, when activated, have enhanced binding of C5a in association with increased mRNA for C5aR. The functional outcome is enhanced release of proinflammatory mediators. These data underscore the phlogistic potential of RAEC and the ability of C5a to enhance the phlogistic responses of RAEC.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Niels C
authors.initials: NC
authors.lastname: Riedemann
authors.forename: Ren-Feng
authors.initials: RF
authors.lastname: Guo
authors.forename: Vidya J
authors.initials: VJ
authors.lastname: Sarma
authors.forename: Ines J
authors.initials: IJ
authors.lastname: Laudes
authors.forename: Markus
authors.initials: M
authors.lastname: Huber-Lang
authors.forename: Roscoe L
authors.initials: RL
authors.lastname: Warner
authors.forename: Eric A
authors.initials: EA
authors.lastname: Albrecht
authors.forename: Cecilia L
authors.initials: CL
authors.lastname: Speyer
authors.forename: Peter A
authors.initials: PA
authors.lastname: Ward
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D054426:Chemokine CXCL2; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000096:biosynthesis; D015936:Complement C5a / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006133:Growth Substances / Q000096:biosynthesis; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000494:pharmacology; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D015846:Monokines / Q000096:biosynthesis; D023282:Nuclease Protection Assays; D011650:Pulmonary Alveoli / Q000166:cytology / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020318:Rats, Long-Evans; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; D054426:Chemokine CXCL2; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C513296:Cxcl2 protein, rat; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D015846:Monokines; D012333:RNA, Messenger; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D014409:Tumor Necrosis Factor-alpha; D015936:Complement C5a