A recombinant fragment of human surfactant protein D lacking the short collagen-like stalk fails to correct morphological alterations in lungs of SP-D deficient mice.
Emphysema-like pathology is a characteristic feature of surfactant protein D (SP-D) knock-out mice. Treatment with a recombinant fragment of human SP-D consisting of a short collagen-like stalk (but not the entire collagen-like domain of native SP-D), neck, and carbohydrate recognizing domain (CRD) inhibits development of emphysema-like pathology in SP-D deficient mice. On the other hand, it has been shown that the entire collagen-like domain is necessary for preventing SP-D knock-out mice from pulmonary emphysema development. Thus, in the present study, we aimed to elucidate the role of the short collagen-like stalk for the function of the recombinant fragment of human SP-D. We treated SP-D knock-out mice with a fragment of human SP-D lacking the short collagen-like stalk and compared the effects on lung morphology with results from untreated wild-type and SP-D knock-out mice and from SP-D knock-out mice treated with a recombinant fragment of human SP-D including the short collagen-like stalk. The fragment of SP-D lacking the short collagen-like stalk failed to correct pulmonary emphysematous alterations demonstrating the importance of the short collagen-like stalk for the biological activity of the recombinant fragment of human SP-D.
Knudsen
Lars
L
Institute of Anatomy, University of Bern, Baltzerstrasse 2, Bern 9, Switzerland.
Wucherpfennig
Katharina
K
Mackay
Rose-Marie
RM
Townsend
Paul
P
Mühlfeld
Christian
C
Richter
Joachim
J
Hawgood
Samuel
S
Reid
Kenneth
K
Clark
Howard
H
Ochs
Matthias
M
D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D011656:Pulmonary Emphysema / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D037663:Pulmonary Surfactant-Associated Protein D / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology
D010446:Peptide Fragments; D037663:Pulmonary Surfactant-Associated Protein D; D011994:Recombinant Proteins