Human recombinant macrophage inflammatory protein-1 alpha and -beta and monocyte chemotactic and activating factor utilize common and unique receptors on human monocytes.
The human macrophage inflammatory proteins-1 alpha and -beta (MIP-1 alpha and -beta), which are also known as LD78 and ACT2, respectively, are distinct but highly related members of the chemoattractant cytokine (chemokine) family. rMIP-1 alpha and -beta labeled with 125I specifically bind to human peripheral blood monocytes, the monocytic cell line THP-1, peripheral blood T cells, and the YT cell line. Steady state binding experiments revealed approximately 3000 high affinity binding sites/cell for MIP-1 alpha on human monocytes and on THP-1 cells, with Kd values of 383 pM and 450 pM, respectively. Human MIP-1 alpha and -beta had nearly identical affinities for the binding sites and each competed equally well for binding. Human monocyte chemotactic and activating factor (MCAF), a member of the same chemokine family, consistently displaced about 25% of human MIP-1 alpha and -beta binding on monocytes but not on YT cells, which did not bind MCAF. On the other hand, human rMIP-1 alpha and -beta partially inhibited binding of radiolabeled MCAF to monocytes. Both MIP-1 alpha and -beta were chemotactic for human monocytes. Preincubation of monocytes with human rMIP-1 alpha or -beta markedly reduced cell migration towards the other cytokine, whereas preincubation with human rMCAF only partially desensitized the monocyte chemotaxis response to human rMIP-1 alpha or -beta. These data suggest the existence of three subtypes of receptors, i.e., one unique receptor shared by MIP-1 alpha and -beta, a second unique receptor for MCAF, and a third species that recognizes both MCAF and MIP-1 peptides.
Wang
J M
JM
Laboratory of Molecular Immunoregulation, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702.
Sherry
B
B
Fivash
M J
MJ
Kelvin
D J
DJ
Oppenheim
J J
JJ
D001665:Binding Sites; D002460:Cell Line; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D002630:Chemotactic Factors / Q000378:metabolism*; D002633:Chemotaxis / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D019402:Macrophage Inflammatory Proteins; D008264:Macrophages / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D015846:Monokines / Q000378:metabolism* / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000032:analysis*; D011994:Recombinant Proteins / Q000378:metabolism
D018932:Chemokine CCL2; D054407:Chemokine CCL4; D002630:Chemotactic Factors; D016207:Cytokines; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D011971:Receptors, Immunologic; D011994:Recombinant Proteins