The cloning and characterization of a murine secretory leukocyte protease inhibitor cDNA.
Human secretory leukocyte protease inhibitor (hSLPI) is produced by epithelial cells at mucosal surfaces, where it regulates both the neutrophil-mediated inflammation that characterizes inflammatory diseases, and pathogens themselves via both antiprotease and "defensin-like" activities. Additionally, hSLPI may regulate other processes such as cutaneous desquamation and placental invasiveness. To better understand the primary physiologic roles of SLPI, it will be important to establish a genetically tractable animal model, the most attractive candidate being the mouse. In this report, the cloning and characterization of murine (m) SLPI is described. mSLPI is encoded by a single copy gene, and appears structurally highly similar to hSLPI. At the same time, significant differences between mSLPI and hSLPI are presented, notably a difference in expression pattern, and a structural difference in the protease binding site that correlates with a difference in the spectrum of protease inhibiton. Such species-specific evolution of this protease inhibitor is notable given that species-specific structure-function differences have previously been reported for the alpha-1 antitrypsin family.
Zitnik
R J
RJ
Department of Internal Medicine, Yale University, New Haven, Connecticut 06520, USA. zitnik@biomed.med.yale.edu
Zhang
J
J
Kashem
M A
MA
Kohno
T
T
Lyons
D E
DE
Wright
C D
CD
Rosen
E
E
Goldberg
I
I
Hayday
A C
AC
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D053481:Secretory Leukocyte Peptidase Inhibitor; D017386:Sequence Homology, Amino Acid; D015842:Serine Proteinase Inhibitors / Q000235:genetics* / Q000378:metabolism; D013045:Species Specificity; D013552:Swine; D014018:Tissue Distribution
D017931:DNA Primers; D018076:DNA, Complementary; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; D015842:Serine Proteinase Inhibitors; C506815:Slpi protein, mouse