title: Surfactant protein A inhibits T cell proliferation via its collagen-like tail and a 210-kDa receptor.
abstract: Investigation of possible mechanisms to describe the hyporesponsiveness of pulmonary leukocytes has led to the study of pulmonary surfactant and its constituents as immune suppressive agents. Pulmonary surfactant is a phospholipid-protein mixture that reduces surface tension in the lung and prevents collapse of the alveoli. The most abundant protein in this mixture is a hydrophilic molecule termed surfactant-associated protein A (SP-A). Previously, we showed that bovine (b) SP-A can inhibit human T lymphocyte proliferation and interleukin-2 production in vitro. Results presented in this investigation showed that different sources of human SP-A and bSP-A as well as recombinant rat SP-A inhibited human T lymphocyte proliferation in a dose-dependent manner. A structurally similar collagenous protein, C1q, did not block the in vitro inhibitory action of SP-A. The addition of large concentrations of mannan to SP-A-treated cultures also did not disrupt inhibition, suggesting that the effect is not mediated by the carbohydrate recognition domain of SP-A. Use of recombinant mutant SP-As revealed that a 36-amino acid Arg-Gly-Asp (RGD) motif-containing span of the collagen-like domain was responsible for the inhibition of T cell proliferation. A polyclonal antiserum directed against an SP-A receptor (SP-R210) completely blocked the inhibition of T cell proliferation by SP-A. These results emphasize a potential role for SP-A in dampening lymphocyte responses to exogenous stimuli. The data also provide further support for the concept that SP-A maintains a balance between the clearance of inhaled pathogens and protection against collateral immune-mediated damage.
authors.affiliation: Department of Medicine, The Lawson Research Institute, St. Joseph's Health Center, The University of Western Ontario, London, Ontario, Canada N6A 4V2.
authors.forename: P
authors.initials: P
authors.lastname: Borron
authors.forename: F X
authors.initials: FX
authors.lastname: McCormack
authors.forename: B M
authors.initials: BM
authors.lastname: Elhalwagi
authors.forename: Z C
authors.initials: ZC
authors.lastname: Chroneos
authors.forename: J F
authors.initials: JF
authors.lastname: Lewis
authors.forename: S
authors.initials: S
authors.lastname: Zhu
authors.forename: J R
authors.initials: JR
authors.lastname: Wright
authors.forename: V L
authors.initials: VL
authors.lastname: Shepherd
authors.forename: F
authors.initials: F
authors.lastname: Possmayer
authors.forename: K
authors.initials: K
authors.lastname: Inchley
authors.forename: L J
authors.initials: LJ
authors.lastname: Fraher
mesh_terms: D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D003094:Collagen; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000502:physiology*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D016296:Mutagenesis; D010446:Peptide Fragments / Q000494:pharmacology*; D011510:Proteolipids / Q000737:chemistry / Q000494:pharmacology / Q000502:physiology*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000737:chemistry / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology; D017384:Sequence Deletion; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
chemical_list: D007376:Interleukin-2; D010446:Peptide Fragments; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C067774:surfactant protein A receptor; D003094:Collagen