Role of the maleyl-albumin receptor in activation of murine peritoneal macrophages in vitro.
It has been previously demonstrated that maley-lated-BSA (maleyl-albumin) induces functional activation in murine peritoneal macrophages. Furthermore, maleyl-albumin has been shown to interact with two distinct sites on human monocytes; one site is the scavenger receptor, a 260-kDa oligomeric protein which recognizes modified forms of low density lipoprotein (LDL), and the second is a lower affinity site which has yet to be structurally characterized. In the present study, we wished to quantitatively assess the number and character of maleyl-albumin-binding sites on murine peritoneal macrophages and to determine which site or sites are involved in signaling the macrophage to undergo extensive functional development. Binding studies. demonstrate at least two distinct receptors for maleyl-albumin on murine peritoneal macrophages. Scatchard analyses of the binding isotherms reveal two sites characterized by dissociation constants (Kd) of 17.6 nM and 4.9 microM and maximal binding of 1.2 x 10(5) and 1 x 10(6) sites/cell, respectively. The contribution of the scavenger receptor, determined by binding analyses of malondialdehyde-LDL, is described by two sites with Kd of 39.4 pM and 9.6 nM, and maximal binding of 2.7 x 10(3) and 1.9 x 10(4) sites/cell, respectively. Maleyl-albumin blocks binding of malondialdehyde-LDL, whereas modified LDL fails to inhibit binding of maleyl-albumin. Maleyl-albumin, at concentrations producing lower affinity binding, stimulates tumor cytolysis, expression of mRNA encoding TNF, and suppression of INF-gamma-induced expression of Ia Ag. Malondialdehyde-LDL fails to elicit these responses. We conclude that macrophage activation produced by maleyl-albumin is mediated by interaction with the low affinity, high capacity binding site for maleyl-albumin rather than the scavenger receptor.
Haberland
M E
ME
Department of Medicine, School of Medicine, University of California, Los Angeles 90024.
Tannenbaum
C S
CS
Williams
R E
RE
Adams
D O
DO
Hamilton
T A
TA
D000418:Albumins / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D008315:Malondialdehyde / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D010529:Peritoneal Cavity; D012333:RNA, Messenger / Q000378:metabolism; D017457:Receptors, Albumin; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D011973:Receptors, LDL / Q000187:drug effects / Q000502:physiology; D012710:Serum Albumin, Bovine / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000418:Albumins; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D017457:Receptors, Albumin; D011956:Receptors, Cell Surface; D011973:Receptors, LDL; D014409:Tumor Necrosis Factor-alpha; C049877:maleylalbumin; D012710:Serum Albumin, Bovine; D008315:Malondialdehyde