Pathogenesis of beta(2)-microglobulin amyloidosis: role of monocytes/macrophages.
beta(2)-microglobulin (beta(2)M) amyloidosis (A beta(2)M) is a serious, often incapacitating complication for patients undergoing long-term hemodialysis. Amyloid deposits composed of beta(2)M fibrils as the major constituent protein are mainly localized in joints and periarticular bone and lead to chronic arthralgias, carpal tunnel syndrome, and eventually destructive arthropathy. Although recent histologic studies have shown the accumulation of monocytes/macrophages around amyloid deposits, the factor(s) causing their infiltration and pathologic involvement have yet to be fully elucidated. Immunohistochemical staining reveals that macrophages in tenosynovial tissues express CD13, CD14, CD33, HLA-DR, and CD68 antigens on their surfaces and express interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha, and IL-6. Many of these cells also express LFA-1 (CD11a/CD18), Mac-1 (CD11b/CD18), and VLA-4 (CD49d/CD29) on their surfaces. AGE-modified beta(2)M enhances chemotaxis of monocytes and stimulates macrophages to release bone-resorbing cytokines, such as IL-1 beta, TNF-alpha and IL-6. Via a RAGE-mediated pathway, AGE-modified, but not unmodified beta(2)M, significantly delays constitutive apoptosis of human peripheral blood monocytes. Monocytes survival in an advanced glycation end product (AGE) beta(2)M-containing microenvironment is associated with their phenotypic alteration into macrophage-like cells that generate more reactive oxygen species and elaborate greater quantities of IL-1 beta and TNF-alpha. Thus through regulation of their survival and differentiation, AGE beta(2)M in amyloid deposits may be able to influence the presence and quantity of infiltrated monocytes, and hence their biologic effects.
Hou
F F
FF
Division of Nephrology, Nanfang Hospital, Guangzhou, Peoples Republic of China.
Reddan
D N
DN
Seng
W K
WK
Owen
W F
WF
D000686:Amyloidosis / Q000209:etiology / Q000378:metabolism*; D002358:Cartilage, Articular / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D003094:Collagen / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D008264:Macrophages / Q000502:physiology*
D017127:Glycation End Products, Advanced; D003094:Collagen