Functional modulation of smooth muscle cells by the inflammatory mediator CAP37.
CAP37, a neutrophil-derived protein, originally identified for its antimicrobial activity is now known to have strong immunoregulatory effects on host cells. Recently, we described its expression and localization within the vascular endothelium associated with atherosclerotic plaques. Since CAP37 is a potent activator of endothelial cells and monocytes, two of the key cellular components of the atherosclerotic plaque, this study was undertaken to determine whether CAP37 had functional effects on smooth muscle cells another important cellular participant in atherosclerosis. Sections from atherosclerotic lesions were stained for the presence of CAP37 and smooth muscle cell alpha actin. The effect of CAP37 on aorta smooth muscle cell migration and proliferation was investigated and the upregulation of adhesion molecules was determined. Immunocytochemistry indicated that CAP37 was present in a subset of smooth muscle cells within atherosclerotic lesions, but was absent in normal vessels. Flow cytometry using double labeling for the proliferation marker Ki-67 and CAP37 demonstrates that CAP37 is mainly expressed in proliferating smooth muscle cells. We show that CAP37 supports migration and proliferation of smooth muscle cells in vitro. Furthermore, CAP37-treated smooth muscle cells expressed higher levels of the cell adhesion molecule ICAM-1 when compared with untreated cells. We suggest that due to its localization to atherosclerotic plaques and its ability to modulate smooth muscle cells, CAP37 may play a role in the progression of this disease.
Gonzalez
Melva L
ML
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190, USA.
Ruan
Xin
X
Kumar
Padmasini
P
Grammas
Paula
P
Pereira
H Anne
HA
D000328:Adult; D000368:Aged; D023181:Antimicrobial Cationic Peptides; D001011:Aorta / Q000166:cytology; D001798:Blood Proteins / Q000032:analysis / Q000494:pharmacology / Q000502:physiology*; D002339:Carotid Arteries / Q000166:cytology; D016893:Carotid Stenosis / Q000473:pathology; D002352:Carrier Proteins / Q000032:analysis / Q000494:pharmacology / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology*; D019394:Ki-67 Antigen / Q000032:analysis; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D020033:Protein Isoforms / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology
C062991:AZU1 protein, human; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D018836:Inflammation Mediators; D019394:Ki-67 Antigen; D020033:Protein Isoforms; D011994:Recombinant Proteins