Serum amyloid A is a chemoattractant: induction of migration, adhesion, and tissue infiltration of monocytes and polymorphonuclear leukocytes.
Serum amyloid A (SAA) is an acute phase protein that in the blood is bound to high density lipoproteins; SAA is secreted mainly by hepatocytes, and its concentration increases in the blood up to 1000 times during an inflammatory response. At present, its biological function is unclear. Since some forms of secondary amyloidosis are caused by deposition in tissues of peptides derived from the SAA and leukocytes seem to be involved in this process, we investigated the effect of human SAA on human monocytes and polymorphonuclear cells (PMN). When recombinant human SAA (rSAA) was used at concentrations corresponding to those found during the acute phase (> 0.8 microM), it induced directional migration of monocytes and polymorphonuclear leukocytes. Preincubation of rSAA with high density lipoproteins blocked this chemoattractant activity for both monocytes and PMN. rSAA also regulated the expression of the adhesion proteins CD11b and leukocyte cell adhesion molecule 1 and induced the adhesion of PMN and monocytes to umbilical cord vein endothelial cell monolayers. When subcutaneously injected into mice, rSAA recruited PMN and monocytes at the injection site. On the basis of these data, we suggest that SAA may participate in enhancing the migration of monocytes and PMN to inflamed tissues during an acute phase response.
Badolato
R
R
Laboratory of Molecular Immunoregulation, Program Resources, Inc./Dyncorp, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702.
Wang
J M
JM
Murphy
W J
WJ
Lloyd
A R
AR
Michiel
D F
DF
Bausserman
L L
LL
Kelvin
D J
DJ
Oppenheim
J J
JJ
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects; D002630:Chemotactic Factors / Q000494:pharmacology*; D006801:Humans; D019041:L-Selectin; D008075:Lipoproteins, HDL / Q000378:metabolism / Q000494:pharmacology; D016177:Macrophage-1 Antigen / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D000685:Serum Amyloid A Protein / Q000494:pharmacology*
D015815:Cell Adhesion Molecules; D002630:Chemotactic Factors; D008075:Lipoproteins, HDL; D016177:Macrophage-1 Antigen; D000685:Serum Amyloid A Protein; D019041:L-Selectin