Mechanisms of anti-influenza activity of surfactant proteins A and D: comparison with serum collectins.
The present study provides the first direct comparison of anti-influenza A virus (IAV) activities of the collectins surfactant protein (SP) A and SP-D, mannose-binding lectin (MBL), and conglutinin. SP-D, MBL, and conglutinin inhibited IAV hemagglutination activity with a greater potency than and by a distinct mechanism from SP-A. Although isolated trimeric SP-D carbohydrate recognition domains inhibited hemagglutination activity, preparations of SP-D also containing the collagen domain and NH2 terminus caused greater inhibition. In contrast to SP-A (or nonmultimerized SP-D), absence of the N-linked attachment did not effect interactions of multimerized SP-D with IAV. SP-D, SP-A, and conglutinin caused viral precipitation through formation of massive viral aggregates, whereas MBL formed aggregates of smaller size that did not precipitate. All of the collectins enhanced IAV binding to neutrophils; however, in the case of MBL, this effect was modest compared with the binding enhancement induced by SP-D or conglutinin. These studies clarify the structural requirements for viral inhibition by SP-D and reveal significant differences in the mechanisms of anti-IAV activity among the collectins.
Hartshorn
K L
KL
Department of Medicine, Boston University School of Medicine, Massachusetts, USA.
White
M R
MR
Shepherd
V
V
Reid
K
K
Jensenius
J C
JC
Crouch
E C
EC
D000818:Animals; D000998:Antiviral Agents; D016466:CHO Cells; D002352:Carrier Proteins / Q000097:blood* / Q000494:pharmacology*; D002642:Chick Embryo; D037222:Collectins; D006224:Cricetinae; D004912:Erythrocytes / Q000821:virology*; D006023:Glycoproteins / Q000494:pharmacology*; D006384:Hemagglutination / Q000187:drug effects; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects* / Q000502:physiology; D008351:Mannans / Q000494:pharmacology; D009504:Neutrophils / Q000821:virology*; D011510:Proteolipids / Q000494:pharmacology*; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology
D000998:Antiviral Agents; D002352:Carrier Proteins; D037222:Collectins; D006023:Glycoproteins; D008351:Mannans; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D011994:Recombinant Proteins