Acute-phase, but not constitutive serum amyloid A (SAA) is chemotactic for cultured human aortic smooth muscle cells.
The human serum amyloid A (SAA) protein family is subclassified as acute phase SAA (A-SAA), which comprises the SAA1 and SAA2 allelic variants, and constitutive SAA (C-SAA), which is the SAA4 isoform. Extrahepatic production of A-SAA occurs in many organs and tissues of the body, including smooth muscle cells (SMC) of the aorta. A-SAA has been shown to act locally as a chemoattractant for neutrophils, monocytes and lymphocytes via the N-formyl peptide receptor-like (fPRL1). In order to gain further understanding of the physiological significance of local production of A-SAA by SMC, the effect of exogenous A-SAA on the in vitro migration of human aortic SMC was investigated. Increased SMC migration in the presence of A-SAA was detectable after six hours and continued to increase up to 24 hours after incubation. The increased migration was dose-dependent over the concentration range 10 to 100 micrograms/ml. The mode of A-SAA stimulated SMC migration was by chemotaxis not chemokinesis. Exogenous constitutive SAA (C-SAA) did not affect SMC migration. Stimulation of SMC migration by A-SAA was inhibited by both polyclonal and monoclonal antibodies to human SAA1 and also by the inhibitors of fPRL1 signaling, wortmannin, bisindolylmaleimide and pertussis toxin. The results herein indicate that A-SAA, but not C-SAA, may serve as an autocrine factor to influence SMC migration in situations of aortic tissue injury and inflammation.
Kumon
Yoshitaka
Y
Second Department of Internal Medicine, Kochi Medical School, Kohasu Okoh-Cho, Nankoku, Kochi 783-8505, Japan. kumony@kochi-ms.ac.jp
Hosokawa
Takanori
T
Suehiro
Tadashi
T
Ikeda
Yukio
Y
Sipe
Jean D
JD
Hashimoto
Kozo
K
D000595:Amino Acid Sequence; D001011:Aorta / Q000166:cytology*; D001053:Apolipoproteins / Q000502:physiology*; D002478:Cells, Cultured; D002633:Chemotaxis / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D000685:Serum Amyloid A Protein / Q000502:physiology*
D001053:Apolipoproteins; D000685:Serum Amyloid A Protein